QUINOLINES AS TYPE IV PHOSPHODIESTERASE INHIBITORS

Abstract: Optionally 6,8-substituted quinolines of formula (I) wherein: R<1> is selected from hydrogen; lower alkyl; cycloalkyl; cycloalkyloxy; cycloalkylamino; cycloalkyl lower alkyl; lower alkoxy; formyl; hydroxy-lower alkyl; carboxyalkyl; optionally substituted aryl, aryloxy, arylamino or aryl lower alkyl; optionally substituted heterocycle, heterocycle-oxy, heterocycle-amino or heterocycle lower alkyl; and R<2> is optionally substituted phenyl, or a pharmaceutically acceptable salt or N-oxide thereof, useful as anti-inflammatory agents, immunosuppressive agents, anti-allograft rejection agents, anti-graft-vs-host disease agents, anti-allergic agents (e.g., asthma, rhinitis and atopic dermatitis), bronchodilation agents, anti-autoimmune agents or analgetic agents.

Description: Quinolines as type IV phosphodiesterase inhibitors BACKGROUND OF THE INVENTION FIELD OF THE INVENTION This invention relates to optionally 6,8-substituted quinolines useful as anti-inflammatory agents, immunosuppressive agents, anti- allograft rejection agents, anti-graft-vs-host disease agents, anti¬ allergic agents (e.g., asthma, rhinitis and atopic dermatitis), broncho- dilation agents, anti-autoimmune agents or analgetic agents, to their precursors, to their preparation and to pharmaceutical compositions using the compounds of the invention. BACKGROUND INFORMATION Cyclic 3' ,5' -adenoεine monophosphate (cAMP) modulates a variety of cellular and physiologic functions in mammals, such as, cell division, endocrine function, and the immune response. The level of cAMP is controlled by a class of enzymes called phosphodiesterases, which enzymatically deactivate cAMP. There are five general types of phospho¬ diesterases, which are categorized according to their function and the type of cell from which they are isolated. For instance, high-affinity phosphodiesterase (PDE III) is isolated from human platelet cells and modulates platelet aggregation. Another type of phosphodiesterase (PDE IV) is found in various tissues but is the predominant form in human leukocytes; this enzyme modulates leukocyte activation and function associated with the immune response and inflammation. Both of these phosphodiesterases implement their control by modulating the cellular level of cAMP in their respective cells. Thus, inhibition of phosphodiesterases provides a method of modulating any cellular and bodily function that is controlled by cAMP. Compounds that are nonspecific phosphodiesterase inhibitors are known, i.e., these compounds inhibit all or multiple types of phosphodiesterases. [See, Beavo, J.A. and D.H. Reifsyder, Trends in Pharm. Science, 11:150-155 (1990); and Nicholson, CD., R.A.J. Challiss and M. Shahid, Trends in Pharm. Science, 12:19-27 (1991).] Since cAMP is involved in so many functions throughout the body, a nonspecific phosphodiesterase inhibitor has the potential to alter all of the functions modulated by cAMP, thus nonspecific phosphodiesterase inhibitors are of limited value because of numerous side-effects. It has been surprisingly discovered that certain optionally substituted 6, 8-quinolines are potent selective inhibitors of Phosphodiesterase Type IV (PDE IV) . These compounds are well suited for use as a treatment for any disorder in which PDE IV function plays a role, such as where leukocyte activation or function is involved. In particular, these compounds are especially well suited for use as anti- inflammatory agents, immunosuppressive agents, anti-allograft rejection agents, anti-graft-vs-host disease agents, anti-allergic agents (e.g., asthma, rhinitis and atopic dermatitis), bronchodilation agents, anti-autoimmune disease agents or analgetic agents. SUMMARY OF THE INVENTION One aspect of the present invention relates to optionally substituted 6, 8-quinolines, i.e., a compound of Formula I: Formula I wherein: R 1 is selected from hydrogen; lower alkyl; cycloalkyl; cycloalkyloxy; cycloalkylamino; cycloalkyl lower alkyl; lower alkoxy; formyl; hydroxy-lower alkyl; carboxyalkyl; optionally substituted aryl, aryloxy, arylamino or aryl lower alkyl; optionally substituted heterocycle, heterocycle-oxy, heterocycle-amino or heterocycle lower alkyl; and R 2 is optionally substituted phenyl, or a pharmaceutically acceptable salt or N-oxide thereof. Preferred aspects of R 1 are pyridylmethyl, benzyl, cycloalkylmethyl and lower alkyl. In another aspect, the invention relates to a pharmaceutical composition containing a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt or N-oxide thereof admixed with at least one pharmaceutically acceptable excipient. In still another aspect, the invention relates to a method of use as an anti-inflammatory agent, immunosuppressive agent, anti-allograft rejection agent, anti-graft-vs-host disease agent, anti-allergic agent (e.g., asthma, rhinitis and atopic dermatitis), bronchodilation agents, anti-autoimmune disease agent or analgetic agent, by administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt or N-oxide thereof. Yet another aspect of the invention relates to the treatment of the above conditions or diseases by the selective inhibition of PDE IV. In another aspect, this invention provides compositions useful in the treatment of inflammatory, allograft rejection, graft-vs-host disease, allergy, autoimmune or analgetic conditions or diseases in mammals comprising a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt or N-oxide as described above and a pharmaceutically acceptable excipient. Another aspect of the invention relates to processes for making the compounds of Formula I and the pharmaceutically acceptable salts and N- oxides thereof. DETAILED DESCRIPTION DEFINITIONS AND GENERAL PARAMETERS The following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein. The term "alkyl" refers to a branched or straight chain monovalent saturated aliphatic hydrocarbon radical of one to twenty carbon atoms. The term "lower alkyl" refers to a branched or straight chain monovalent alkyl radical of one to four carbon atoms. This term is further exemplified by such radicals as methyl, ethyl, n-propyl, isopropyl, i-butyl, n-butyl and t-butyl. The term "cycloalkyl" refers to a monovalent carbocyclic radical of three to six carbon atoms, i.e., cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, which can optionally be substituted, independently, with, e.g., hydroxy, amino, imino, lower alkyl, lower alkoxy, carboxy, lower alkoxycarbonyl, carbamoyl, acyl, aryl, halo, and/or cyano. The term "cycloalkyloxy" refers to a cycloalkyl group attached to a parent structure via an oxy radical, i.e., -0-, such as cyclopentyloxy. The term "cycloalkylamino" refers to a cycloalkyl group attached to a parent structure via an imino radical, i.e., -NH-, such as cyclopropylamino. The term "cycloalkyl lower alkyl" refers to a cycloalkyl group attached to a parent structure via a lower alkylene group such as methylene; e.g., cyclopropylmethyl, cyclopentylethyl, cyclopentylpropyl, or cyclopentylmethyl. The term "lower alkylene" refers to a biradical branched or unbranched saturated hydrocarbon chain containing 1 to 4 carbon atoms, such as methylene (-CH 2 -) , ethylene, propylene, isopropylene and butylene. The term "lower alkoxy" refers to the group -0-R' where R' is lower alkyl. The term "carbonyl" refers to the group -C(0)-. The term "carboxy" refers to the group -C(0)OH. The term "carboxyalkyl" refers to the group -alkyl-C(0)OH, where alkyl is a branched or straight chain monovalent alkyl radical of one to eight carbon atoms. The term "lower alkoxycarbonyl" refers to the group -C(0)OR' where R 1 is lower alkyl. The term "acyl" refers to the group -C(0)-R', where R 1 is lower alkyl, e.g., acetyl or propionyl; or optionally substituted phenyl or heterocycle, e.g., phenacyl. The term "carbamoyl" refers to the group -C(0)NR'R where R and R' are independently hydrogen or lower alkyl, e.g., where R is hydrogen and R' is lower-alkyl the group is lower alkylcarbamoyl, where R and R' are lower alkyl the group is di-lower alkylcarbamoyl. The term "halo" refers to fluoro, bromo, chloro and iodo. The term "lower alkylthio" refers to the group R-S- . The term "lower alkylsulfinyl" refers to the group R-S(O)-. The term "lower alkylsulfonyl" refers to the group R-S(0) 2 -. The term "lower alkoxyεulfonyl" refers to the group RO-S(0) 2 -. The term "hydroxyεulfonyl" refers to the group HO-S(0 2 )-. The term "aryl" refers to a monovalent carbocyclic aromatic radical (e.g., phenyl), or two condensed carbocyclic rings (e.g., naphthyl) which can optionally be mono-, di-, or tri-substituted, independently, with hydroxy, thiol, amino, halo, nitro, lower alkyl, lower alkylthio, lower alkoxy, mono-lower alkylamino, di-lower alkylamino, carboxy, lower alkoxycarbonyl, hydroxysulfonyl, lower alkoxysulfonyl, lower alkylsulfonyl, lower alkylsulfinyl, trifluoromethyl, cyano, tetrazolyl, carbamoyl, lower alkylcarbamoyl, and di-lower alkylcarbamoyl. The term "aryloxy" refers to an aryl group as defined above attached to a parent structure via an oxy radical, i.e., aryl-O-. The term "arylamino" refers to an aryl group as defined above attached to a parent structure via an imino radical, i.e., aryl-NH-. The term "aryl lower alkyl" refers to an aryl group attached to a parent structure via a lower alkylene group such as methylene; e.g., benzyl. The term "heterocycle" refers to a saturated, unsaturated or aromatic monovalent cyclic radical having at least one hetero atom (such as nitrogen, oxygen or sulfur) or a combination thereof, which can optionally be substituted, independently, with, e.g., hydroxy, amino, imino, lower alkyl, lower alkoxy, carboxy, lower alkoxycarbonyl, carbamoyl, acyl, aryl, halo, and/or cyano. Further, the term also includes instances where an atom of a heterocycle has been oxidized, e.g., N-oxides, sulfoxides, sulfones, or oxo. For example, typical heterocycles with one or more nitrogen or sulfur atoms are pyrrole, imidazole, imidazoline, imidazolidine, pyrazole, pyrazine, pyrrolidine, pyrrolidinone, pyrazolidme, piperidme, piperazine, 5 morpholine, pyridine, pyridone, triazole, oxazole, oxadiazole, thiazole, and the like. The term "heterocycle-oxy" refers to a heterocyclic group as defined above attached to a parent structure via an oxy radical, i.e., heterocycle-0- . 10 The term "heterocycle-amino" refers to a heterocyclic group as defined above attached to a parent structure via an imino radical, i.e., heterocycle-NH- . The term "heterocycle lower alkyl" refers to a heterocyclic group attached to a parent structure via a lower alkylene group such as 15 methylene (-CH 2 -); e.g., 4-pyridylmethyl. The term "tetrazolyl" refers to the group NH 20 N~N The term "optionally substituted phenyl" refers to phenyl and mono-, di-, tri- or tetra-substituted phenyl, wherein the optional εubstituents are lower alkyl, hydroxy, thiol, amino, halo, nitro, cyano, lower alkoxy, 25 lower alkylthio, mono-lower alkylamino, di-lower-alkylamino, carboxy, lower alkoxycarbonyl, lower, alkylene-dioxy, hydroxysulfonyl, lower alkoxyεulfonyl, lower alkylεulfonyl, lower-alkylεulfinyl, trifluoromethyl, trifluoromethyloxy, tetrazolyl, carbamoyl, lower alkylcarbamoyl, and di- lower alkylcarbamoyl. Thiε term is further exemplified by such radicals as 30 3-chlorophenyl, 3-nitrophenyl, 4-methoxyphenyl, 3-cyanophenyl, 4- trifluorophenyl, 3-chloro-4-fluorophenyl and 3,4-methylenedioxyphenyl. The term "N-oxide" refers to nitrogen heterocycles where a nitrogen atom in the ring has been oxidized, e.g., 4-pyridyl-N-oxide, 3-pyridyl-N-oxide, or 2-pyridyl-N-oxide. 35 The term "hydroxy-lower alkyl" refers to a lower alkyl radical substituted with a hydroxy group, e.g., -CH(OH)CH 2 CH 3 or -C(OH) (CH 3 ) 2 . The term "pharmaceutically acceptable εalt" refers to any salt derived from an inorganic or organic acid or base. The term "pharmaceutically acceptable anion" refers to the anion of V 40 such acid addition salts. The term "pharmaceutically acceptable cation" refers to the cation of such base addition εalts. The salt, anion and/or the cation are choεen not to be biologically or otherwiεe undesirable. The anions are derived from inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid (giving the sulfate and biεulfate salts) , 45 nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, alonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, salicylic acid, p-toluenesulfonic acid and the like. The cations are derived from bases, such as alkaline earth hydroxides, including calcium hydroxide, potassium hydroxide, sodium hydroxide, lithium hydroxide and the like. As used herein, the term "allograft rejection" refers to the humoral or cellular immune reεponεe mounted by the immune εystem of a mammal after it has received a histo-incompatible tissue graft from another mammal of the same species, thereby producing tissue injury to the graft in such a recipient. As used herein, the term "graft-vs-host disease" refers to the immune response that originates from transplanted graft tissue, in particular, transplanted bone-marrow tissue, and that is directed towards the host tisεue, thereby producing tiεεue injury in the hoεt. As used herein, the term "autoimmune diseaεe" refers to disorders wherein the immune system of a mammal mounts a humoral or cellular immune response to the mammal's own tiεεue or to antigenic agentε that are not intrinsically harmful to the mammal, thereby producing tiεεue injury in εuch a mammal. Examples of such disorders include, but are not limited to, syεtemic lupus erythematosus, rheumatoid arthritis and type I diabetes. As used herein, the terms "treatment" or "treating" of a condition and/or a disease in a mammal, means: (i) preventing the condition or diεeaεe, that is, avoiding any clinical symptomε of the disease; (ii) inhibiting the condition or disease, that is, arresting the development or progresεion of clinical symptoms; and/or (iii) relieving the condition or disease, that is, causing the regression of clinical symptoms. The conditions and diseases treated in the present invention include inflammation, pain, pyrexia, autoimmune disease, allograft rejection, graft-vs-host disease, allergies and uveitis. As used herein, the term "therapeutically effective amount" refers to that amount of a compound of Formula I which, when administered to a mammal in need thereof, is sufficient to effect treatment (as defined above) as an anti-inflammatory agent, immunosuppreεsive agent, anti-allograft rejection agent, anti-graft-vs-host disease agent, anti-allergy agent, autoimmune diseaεe agent or analgetic agent. The amount that conεtitutes a "therapeutically effective amount" will vary depending on the compound, the condition or disease and its severity, and the mammal to be treated, but may be determined routinely by one of ordinary skill in the art with regard to contemporary knowledge and to this disclosure. As used herein, the term "q.s." means adding a quantity sufficient to achieve a εtated function, e.g., to bring a solution to a desired volume (e.g. , 100 mL) . As used herein, the term "mp" refers to melting point. All temperatures are given in degrees Celsius CO . Unless specified to the contrary, the reactions described herein take place at atmospheric pressure over a temperature range from about -78°C to about 150°C, more preferably from about 10°C to about 50°C, and most preferably at about room (or "ambient") temperature, e.g., about 20°C. Unless specified to the contrary, the ranges of time and temperature described herein are approximate, e.g., "from 8 to 24 hours at from 10°C to 100°C" means from about 8 to about 24 hours at about 10°C to about 100°C. Iεolation and purification of the compoundε and intermediateε described herein can be effected, if desired, by any suitable separation or purification procedure such aε, for example, filtration, extraction, crystallization, column chromatography, preparative high pressure liquid chromatography (preparative HPLC) , thin-layer chromatography or thick-layer chromatography, or a combination of these procedureε. Specific illustrations of suitable separation and isolation procedureε can be had by reference to the exampleε hereinbelow. However, other equivalent εeparation or iεolation procedureε can also be used. The following numbering and nomenclature system will be used for naming the compounds of the invention. E.g., the compound of Formula I where R 1 is 4-pyridylmethyl and R 2 is 3-chloro-4-fluorophenyl can be named 6- (4-pyridylmethyl) -8- (3- chloro-4-fluorophenyl) quinoline. The compound of Formula I where R 1 is isopropyl and R 2 is 4-chlorophenyl can be named 6- (isopropyl) -8- (4-chlorophenyl)quinoline. SYNTHESIS OF THE COMPOUNDS OF FORMULA I As used in the Reaction Schemeε R 1 and R 2 are the same as described in the Summary of the Invention. Reaction Scheme A illustrates the preparation of 6, 8- (disubstituted) quinolineε, i.e., the compounds of Formula I. Reaction Scheme A-l illustrates the preparation of intermediates of formula 3a which can be converted into compounds of formula I where R 1 is cycloalkylmethyl, arylmethyl or heterocycle-methyl by following the reactions as shown in Reaction Scheme A. Reaction Scheme B illustrates an alternate preparation of 6,8- (disubstituted) quinolines, i.e., the compounds of Formula I, where the final two steps in Reaction Scheme A are carried out in reverse order. Reaction Scheme B-l illustrates an alternate preparation of 6, 8- (disubstituted) quinolines, i.e., the compounds of Formula I, via the 8-ZnCl-quinoline intermediate. Reaction Scheme B-2 illustrates the preparation of 6-subεtituted-8-haloquinolines, in particular, the compounds of Formula 5 where X is halo and R 1 is cycloalkylaminomethyl, arylaminomethyl, heterocycle-aminomethyl or heterocycle-methyl, i.e., where the methylene group is attached to a nitrogen atom of a heterocycle. Reaction Scheme B-3 illustrates the preparation of 6, 8- (disubstituted) quinolines, in particular, the compounds of Formula I where R 1 is cycloalkyloxy, aryloxy or heterocycle-oxy. Reaction Scheme C illustrates the preparation of 6- [lower alkyl- (hydroxy)methyl] -8-quinolines, and 6-formyl-8-quinolines, i.e., the compounds of Formula I where R 1 is formyl, or lower alkyl- (hydroxy)methyl. Reaction Schemes C-l and C-2 illustrate alternate preparations of 6, 8- (disubεtituted) quinolineε, in particular, the compoundε of Formula I where R 1 is alkyl, cycloalkylmethyl, cycloalkenylmethyl, arylmethyl or heterocycle-methyl. Reaction Scheme C-3 illustrates an alternate preparation of 6,8- (disubstituted)quinolines, in particular, the compounds of Formula I where R 1 is mono- or di-alkylaminomethyl, cycloalkylaminomethyl, arylaminomethyl, heterocycle-aminomethyl or heterocycle-methyl, i.e., where the methylene group is attached to a nitrogen atom of a heterocycle. REACTION SCHEME A CO C2} 3 where X is chloro, bromo or i odo 3D R where R is optional ly «D substituted phenyl Formu la I REACTION SCHEME A-l where R is alkyl . cycloalkyl , where X i s aryl I ower al yl or ch Ioro or bromo heterocycle lower alkyl STARTING MATERIALS Referring to the Reaction Schemes, the compounds of Formula 1 (i.e., 4-optionally substituted nitrobenzene) and Formula 2 (i.e., 4-optionally substituted aniline) are commercially available from Aldrich Chemicals Co., Inc., Fluka Chemical Corporation, Lancaster Synthesis Ltd., Karl Industries, Maybridge Chemical Co. Ltd. or Tokyo Kasai International. The compounds of Formula 3A, i.e., optionally substituted benzene boronic acid, are commercially available from Lancaster Synthesiε Ltd. , or alternatively can be prepared following the procedureε in Organic Synthesis, Coll Vol 4. Those compounds that are not commercially available can be prepared by one of ordinary skill in the art following procedures set forth in references such as, "Fieser and Fieεer'ε Reagentε for Organic Synthesis", Volumes 1- 15, John Wiley and Sons, 1991; "Rodd's Chemistry of Carbon Compounds", Volumes 1-5 and Supplementals, Elservier Science Publishers, 1989; and "Organic Reactions", Volumes 1-40, John Wiley and Sons, 1991. PREPARATION OF FORMULA 2 An optionally substituted p-nitrobenzene is combined with about 5 molar equivalents of a reducing agent, such aε SnCl^H , Fe/acetic acid, or palladium on carbon/H 2 , preferably SnClj-H , in a εolvent such as ethanol, or ethyl acetate, preferably ethanol. The solution is heated. The temperature and duration will vary according to the reagent and solvent uεed, e.g., uεing ethanol and SnCl 2 -H 2 0, the solution is heated at a temperature in the range of about 50°C to 90°C, preferably about 70°C, for a period of about 1 hour to 3 hours, preferably about 2 hours. The progress of the reaction is monitored by TLC (thin layer chromatography) . When the reaction is εubstantially complete, the product is isolated and purified by conventional meanε yielding the desired optionally substituted p-aminobenzene compound (i.e., a compound of Formula 2) . PREPARATION OF FORMULA 3 A solution of about 1 molar equivalent of a halogenating agent, such as N-bromosuccinimide (NBS) , or N-chloroεuccinimide (NCS) , preferably N- bromosuccinimide, in a solvent, preferably DMF is added in a gradual manner to a solution of an optionally substituted p-aminobenzene compound (Formula 2) dissolved in a solvent (such as DMF, preferably DMF) . The reaction mixture is stirred at about room temperature for a period of about 1 to 5 hours, preferably about 3 hours. When the reaction is substantially complete (by TLC) , the product is isolated and purified by conventional meanε yielding the deεired optionally εubεtituted p-amino-m-halobenzene compound (i.e., a compound of Formula 3 where X iε chloro or bromo) . PREPARATION OF FORMULA 4 An optionally εubεtituted p-amino-m-halobenzene compound (Formula 3) is combined with about 1 to 5 molar equivalent, preferably about 2 molar equivalent, of an optionally substituted benzene boronic acid, i.e., Formula 3B where R 2 iε optionally substituted phenyl, 2 M Na 2 C0 3 (about 4 molar equivalent) , methanol or ethanol, preferably ethanol, and benzene or toluene, preferably benzene. To this solution is added about 0.01 to 0.1 molar equivalent, preferably about 0.035 molar equivalent, of palladium tetrakis triphenylphosphine. The reaction mixture is heated at about reflux for a period of about 3 to 9 hours, preferably about 6 hours. When the reaction is εubstantially complete (by TLC) , the product iε isolated and purified by conventional means yielding the desired optionally εubεtituted p-amino-m-arylbenzene compound (e.g., a compound of Formula 4) . PREPARATION OF FORMULA I An optionally substituted p-amino-m-arylbenzene compound (Formula 4) is combined with about 1 molar equivalent of an oxidant, such as ferric oxide, m-nitrobenzenesulphonic acid, nitrobenzene, iron(II) sulfate (heptahydrate) /nitrobenzene or arsenic pentoxide, preferably arsenic pentoxide, and 3 molar equivalent of glycerol under an inert atmosphere. The mixture is heated at a temperature in the range of about 75°C to 125°C, preferably about 100°C, for a period of about 15 minutes to 45 minutes, preferably about 30 minutes. About 12 molar equivalent of a concentrated acid (preferably concentrated H 2 S0 4 ) iε added to the mixture in a gradual manner, and the mixture is heated at a temperature in the range of about 100°C to 200°C, preferably about 150°C for a period of about l to 3 hours, preferably about 2 hours. The progress of the reaction is monitored by TLC (9:1 hexane:ethyl acetate) . When the reaction is substantially complete (by TLC) , the product iε isolated and purified by conventional means yielding the desired 6-optionally substituted-8-arylquinoline compound (i.e., a compound of Formula I) . REACTION SCHEME B 3D 53 where X is chlorc bromo or iodo Formula I REACTION SCHEME B-1 5D Formu I a I wnere X is c loro ; where R 2 iε bromo or i odo optional ly substituted phenyl REACTION SCHEME B-2 where X is where R i s I ower c h I oro . a I y I , eye I oa I y I . i πdepe ndent I y bromo. or aryl or hetero¬ I ower a I ky I or ary I ; i odo cycle or Rp is heterocycle REACTION SCHEME B-3 5) where R is lower alkyl, cycloalky l., aryl or heterocycle, and X is chloro . bromo or i odo PREPARATION OF FORMULA 5 An optionally substituted p-amino-m-halobenzene compound (Formula 3) combined with about 1 molar equivalent of arsenic pentoxide and 3 molar equivalent of glycerol under an inert atmosphere. The mixture is heated at a temperature in the range of about 75°C to 125°C, preferably about 100°C, for a period of about 15 minutes to 45 minutes, preferably about 30 minutes. About 12 molar equivalent of a concentrated acid (preferably concentrated H 2 S0 4 ) iε added to the mixture in a gradual manner, and the mixture is heated at a temperature in the range of about 100°C to 200°C, preferably about 150°C for a period of about 1 to 3 hours, preferably about 2 hours. When the reaction is substantially complete (by TLC) , the product is isolated and purified by conventional means yielding the desired 6-optionally substituted-8-haloquinoline compound (i.e., a compound of Formula 5) . PREPARATION OF FORMULA 3B About 2 molar equivalents of trimethylborate iε dissolved in an apolar solvent (such as diethyl ether, or tetrahydrofuran, preferably diethyl ether) and cooled at a temperature in the range of about -50 to -80°C, preferably about -65°C. An optionally substituted phenyl Grignard reagent is added to the solution in a gradual (e.g., dropwise) manner over a period of about 20 minutes/molar equivalent. The mixture iε then εtirred at a temperature in the range of about -50°C to -80°C for about 15 to 45 minuteε, preferably about 30 minuteε. The mixture iε allowed to warm to about -10°C to 10°C, preferably about 0°C and εtirred for a period of about 1 hour. Water iε added to the reaction mixture and the mixture is εtirred for a period of about 1 hour. The organic layer is removed and the residue is extracted (e.g., 3 x ethyl acetate). The organic layers are combined and dried over a drying agent (e.g., MgS0 4 ) . The εolution is concentrated, hexanes are added to the solution and the solution iε stirred for a period of about 1 hour until a free flowing εuεpension form . The εuεpenεion iε filtered and air dried. The reεultant optionally εubεtituted benzene boronic acid (i.e., a compound of Formula 3B) is carried on to the next step of the procesε. PREPARATION OF FORMULA 3C An optionally substituted phenol is dissolved in an aprotic solvent (such as CH 2 C1 2 or THF, preferably CH 2 C1 2 ) and cooled to 0 C. About 5 molar equivalents of triethylamine are added, followed by about 1.5 molar equivalents of trifluoromethaneεulfonic anhydride (triflic anhydride) (e.g., via addition funnel) under nitrogen over a period of 15 min to 60 min, preferably 30 min. The solution is poured into a saturated NaHC0 3 solution and extracted with an aprotic εolvent such as CH 2 C1 2 . The organic layer is washed with water (2 x) , and brine (100 itiL) , dried over a drying agent (e.g., MgS0 4 ) , filtered, and concentrated. Flash chromatography using 10-50%, preferably 20%, ethyl acetate/hexaneε provides a slightly impure brown oil which can be distilled under vacuum to give the trifluoromethanesulfonyloxy derivative (triflate) aε a yellow liquid. PREPARATION OF FORMULA I An 6-optionally subεtituted-8-haloquinoline compound (i.e., a compound of Formula 5) iε combined with about 2 molar equivalent of an optionally substituted benzene boronic acid, i.e., Formula 3A, 2 M Na 2 C0 3 (about 4 molar equivalent), methanol, and benzene. To this εolution iε added about 0.1 molar equivalent of palladium tetrakiε triphenylphosphine. The reaction mixture is heated at about reflux for a period of about 3 to 9 hourε, preferably about 6 hourε. The progress of the reaction iε monitored by TLC. Upon completion of the reaction, the mixture is allowed to cool to about room temperature, and the solventε are removed. About 40 mL/molar equivalent of ethyl acetate iε added to the reεidue and filtered through a drying agent (e.g., Na 2 S0 4 ) . The product is isolated by chromatography, preferably preparative thin layer chromatography, yielding the desired 6-optionally substituted-8-aryl-quinoline compound (i.e., a compound of Formula I) . REACTION SCHEME C Formula I Formu I a I where R is optiona l ly where X is c I oro, subst ituted phenyl brorao or i odo Formu I a I Formu I a I where R is f or y I where X Is chloro, bromo or i odo Formu l a I where R i s for my I Formu I a where R ' is -CCOH^-R and R is I ower a lky l REACTION SCHEME C-l where X is chloro, where R is cycloalkenyl brorao or i odo ary l or heterocycle REACTION SCHEME C-2 where R is al yl , where X is ch loro, cycloalkyl , bromo or iodo or heterocy c I e Formula I where R is opt iona l ly where R is alkyl, subst ituted pheny l cycloalkyl or heterocycle REACTION SCHEME C-3 where X is where R is lower c loro or al yl, eye I oa I y I i ndependeπt l y bromo ary I or hetero¬ I ower alkyl or ary l j cyc I e or NR 2 iε heterocycle PREPARATION OF FORMULA I WHERE R 1 IS -CH j -X AND/OR -CH-.^ A 6-methyl-8-optionally substituted phenyl-quinoline (i.e., a compound of Formula I where R' is methyl, prepared according procedures described in Reaction Scheme A or B) is dissolved in a solvent such as carbon tetrachloride and heated under reflux. About 1 molar equivalent of a halogenating reagent, such as N-bromosuccinamide (NBS) or N- chlorosuccinamide (NCS) , preferably N-bromosuccinamide and about 0.2 molar equivalent of 2,2 ' -azobiε(2-methylpropionitrile) are added to the refluxing εolution. The reaction mixture iε optionally exposed to light (e.g., 250 W light bulb) for a period of about 30 minutes to 90 minutes, preferably about 1 hour. The reaction mixture is then stirred for a period of about 1 to 3 hours, preferably about 2 hourε. The progress of the reaction is monitored by TLC. Upon conversion of greater than about 90% of the starting material, the reaction solution iε cooled to about 0°C, then poured through a drying agent, such as Na 2 S0 4 . The solution iε concentrated yielding the mono- and di-halogenated products (i.e., Formula I, where R 1 iε CH 2 -X and - CH-X 2 ) which are taken on to the next step without further purification or isolation. PREPARATION OF FORMULA I WHERE R 1 IS FORMYL The mono and dihalogenated quinoline mixture from the previous step is disεolved in a εolvent, εuch aε methylene chloride or chloroform, preferably chloroform, and added in a gradual manner to an oxidizing reagent, such as about 5 molar equivalents of tetra n-butylammonium dichromate in a εolvent, such aε methylene chloride or chloroform, preferably chloroform. The reaction mixture iε heated, preferably at reflux temperature, and refluxed for about 2 to 6 hourε, preferably about 4 hours. The reaction mixture is allowed to cooled to about room temperature and filtered, preferably through a silica gel pad. The residue is eluted with an ether, preferably diethyl ether, and isolated and purified by chromatography to obtain the desired 6-formyl-8- (optionally substituted phenyl)quinoline (i.e., Formula I where R 1 if formyl) . Alternatively, the mono and di-halogenated quinoline mixture can be oxidized by the Kornblum oxidation [C em Rev, Vol 67, No. 3, (1967), p 247- 260] or the Sommelet oxidation [Org. React . , Vol 8, p 197-217 (1954)] . PREPARATION OF FORMULA I WHERE R 1 IS -CH(OH) - (LOWER ALKYL) A 6-formyl-8- (optionally εubstituted phenyl)quinoline is diεεolved in a nonpolar εolvent, preferably tetrahydrofuran, and cooled to a temperature in the range of about -50°C to -100°C, preferably about -78°C. To thiε εolution iε added an alkylation reagent, such aε a lower-alkyl Grignard reagent, or a lower-alkyl lithium reagent (about 1 to 3 molar equivalent, preferably about 2 molar equivalent) in a gradual manner. The reaction mixture iε εtirred for a period of about 10 to 30 minutes, preferably about 20 minutes. The reaction mixture is then quenched with an aqueouε salt εolution, preferably εaturated ammonium chloride. The desired product iε purified by extraction (preferably with ethyl acetate) , and drying (preferably over MgS0 4 ) . The reεidue is further purified and isolated by chromatography to yield the deεired optionally substituted 6- [(lower alkyl (hydroxy)methyl] -8- (optionally substituted phenyl)quinoline, i.e., Formula I where R 1 iε lower alkyl (hydroxy)methyl. PREPARATION OF THE SALT OF FORMULA I The pharmaceutically acceptable salts of Formula I are prepared by dissolving a compound of Formula I in a suitable solvent (such as methanol, dioxane or diethyl ether) adding 1 to 3 molar equivalents (preferably about two molar equivalent) of an appropriate acid (such as hydrogen chloride gas) or base (such aε an alkaline earth hydroxide, e.g., lithium hydroxide, calcium hydroxide, potassium hydroxide, sodium hydroxide or the like; preferably sodium hydroxide) and stirring. The εalt is isolated by lyophilization or by precipitation, using techniques that will be apparent to thoεe εkilled in the art. PREPARATION OF N-OXIDES OF FORMULA I A compound of Formula I, where R' iε pyridylmethyl (e.g., 4- pyridylmethyl, 3-pyridylmethyl or 2-pyridylmethyl) , iε converted to the correεponding N-oxide derivative by treating it with an oxidizing agent (e.g., m-chloroperoxybenzoic acid) in a solvent (e.g., methylene chloride) . The solution is stirred for a period of about 30 to 90 minutes, preferably about 60 minuteε at a temperature in the range of about 0°C to 50°C, preferably about room temperature. Following the reaction, the deεired product iε iεolated and purified by preparative thin-layer chromatography. PREFERRED COMPOUNDS Presently preferred are the compounds of Formula I where R 2 is 3-chlorophenyl, 3-nitrophenyl, 3-cyanophenyl or 3-chloro-4-fluoro- phenyl. Of the compounds where R 2 is 3-chlorophenyl, 3-nitrophenyl or 3- cyanophenyl most preferred are the compoundε of Formula I where and R' iε 4-pyridylmethyl, benzyl, ethyl, n-propyl, iεopropyl, n-butyl or 1-hydroxy- 1-methylethyl. Of the compoundε where R 2 is 3-chloro-4-fluorophenyl most preferred are the compounds of Formula I where R ! is 4-pyridylmethyl, benzyl, ethyl, n-propyl, isopropyl, n-butyl or 1-hydroxy-1-methylethyl. PREFERRED PROCESSES A preferred process for making 6-optionally subεtituted 8-aryl- quinolines iε combining the corresponding optionally substituted benzene boronic acid with the corresponding 6-optionally subεtituted quinoline. Another preferred proceεε for making 6-optionally substituted 8-aryl- quinolineε iε combining the corresponding optionally substituted p-amino-m- benzene with glycerol and arsenic pentoxide. Other preferred proceεεeε for making 6-optionally εubstituted 8-aryl- quinolineε are εhown in Reaction Schemeε C, C-l, C-2, and C-3. LAST STEPS The compounds of this invention are prepared according to the following processes: A procesε for the preparation of a compound of the formula Formu I a I wherein: R 1 iε εelected from hydrogen; lower alkyl; cycloalkyl; cycloalkyloxy; cycloalkylamino; cycloalkyl lower alkyl; lower alkoxy; formyl; hydroxy-lower alkyl; carboxyalkyl; optionally subεtituted aryl, aryloxy, arylamino or aryl lower alkyl; optionally substituted heterocycle, heterocycle-oxy, heterocycle-amino or heterocycle lower alkyl; and R 2 is optionally substituted phenyl, provided that when R 1 is methoxy, R 2 is not 4-nitrophenyl or 4- aminophenyl; or a pharmaceutically acceptable εalt or N-oxide thereof, which compriεeε (a) reacting a compound of the formula (4) where R 1 and R 2 are as defined above, with glycerol in the presence of an oxidant; or (b) reacting a compound of the formula (5) where X iε chloro, bromo or iodo, with a boronic acid of the formula (3B) R 2 -B(OH). where R 2 is optionally substituted phenyl; or (c) reacting a compound of the formula where R 1 iε aε defined above, with a trifluoromethane- εulfonyloxy benzene of the formula (3C) R 2 -OTf where R 2 iε optionally εubεtituted phenyl, and -OTf is trifluoro- methanesulfonyloxy; or (d) reacting a compound of the formula (5) where R iε lower alkyl, cycloalkyl, aryl, or heterocycle, with a boronic acid of the formula (3B) R 2 -B(OH) 2 where R 2 iε optionally εubstituted phenyl; or (e) reacting a compound of the formula (I) where R 2 is optionally subεtituted phenyl, with a lower alkyl Grignard reagent or a lower alkyl lithium reagent; or (f) reacting a compound of the formula where R 2 iε optionally subεtituted phenyl, with a boronic acid of the formula (3B) R-B(OH) 2 where R iε cycloalkenyl, aryl or heterocycle; or (g) reacting a compound of the formula where R 2 is optionally εubεtituted phenyl, and R iε alkyl, cycloalkyl or heterocycle, with a concentrated acid; or (h) reacting a compound of the formula where R, iε optionally εubstituted phenyl and X iε chloro, bromo or iodo, with a compound of the formula where R is lower alkyl, cycloalkyl, aryl or heterocycle; and R^ is independently lower alkyl or aryl; or NRj is heterocycle; or (i) reacting the free base of a compound of Formula I with an acid to give a pharmaceutically acceptable acid addition salt; or (j) reacting an acid addition salt of a compound of Formula I with a baεe to give the correεponding free base; or (k) converting an acid addition salt of a compound of Formula I to another pharmaceutically acceptable acid addition salt of Formula I. UTILITY, TESTING AND ADMINISTRATION GENERAL UTILITY The compounds of this invention, including the pharmaceutically acceptable saltε and N-oxides thereof, and the compositions containing them are particularly useful aε anti-inflammatory, immunosuppressive, anti- allograft rejection, anti-graft-vs-hoεt diεeaεe, anti-allergic agents (e.g., asthma, rhinitis and atopic dermatitis), bronchodilation agents, anti-autoimmune diεeaεe or analgetic agentε. The compoundε of this invention act as PDE IV selective inhibitors, thereby modulating cAMP levelε. Thuε, theεe compounds are of use for the treatment of cAMP related conditions or diεeaεeε, particularly thoεe that are modulated by leukocyte CAMP. For example, inflammation, autoimmune diεeases, graft-vs-hoεt disease and allograft rejection are conditions that are manifested by the proliferation of lymphocytes. The proliferation iε triggered by the presence of cAMP at specific levelε. Inhibition of lymphocyte proliferation iε accomplished by increasing levels of cAMP resulting from the inhibition of lymphocyte phosphodieεteraεe. TESTING Potency and selectivity of compounds as inhibitors of PDE IV is determined by following, for example, the procedures described in Example 22, or modificationε thereof. The immunomodulatory and anti-inflammatory activity of the compounds of the invention can be determined by a variety of assays utilizing both in vitro and in vivo procedures. Inhibition of the proliferation of lymphocytes in responεe to mitogenic εtimulation is determined by the procedures described by Greaves, et al. ["Activation of human T and B lymphocytes by polyclonal mitogens," Nature, 248, 698-701 (1974)], or modificationε thereof (Example 23) . Inhibition of lymphocyte activation in reεponεe to antigenic challenge iε determined in vi tro by inhibition of a cytolytic T-cell aεεay (CTL) as described by Wunderlich, et al. , Nature (1970), Vol. 228, p. 62, or a modification thereof. Immune modulation is determined by in vivo procedures utilizing the Jerne Hemolytic Plaque Assay, [Jerne, et al., "The agar plaque technique for recognizing antibody producing cells," Cell-bound Antibodies, Amos, B. and Kaprowski, H. editorε (Wistar Institute Preεε, Philadelphia) 1963, p. 109] or a modification thereof (Example 24) . Anti-inflammatory activity is determined by the Arachidonic Acid-Induced Mouse Ear Edema Aεsay [Young, et al. , J. Invest . Derm. , 82 : 367-371 (1984)] (Example 25) . Anti-inflammatory activity is also determined by the Adjuvant Arthritis assay [Pearson, C ., Proc. Soc. Exp . Biol . Med. , 51:95-101 (1956)] , or modifications thereof (Example 26) . Anti-autoimmune activity in treating autoimmune diεease can be determined utilizing the survivability of MRL/lpr mice described by Theofilopouloε, et al. , Advances in Immunology, Vol 37, pageε 269-390 (1985) on pageε 274-276, or a modification thereof (Example 27) . Analgetic activity iε determined by the Phenylquinone-induced Mouεe Writhing Assay [Hendershot, et al. , J. Pharmacol . Exp . Ther. , 125: 237-240 (1959)] (Example 28) . ADMINISTRATION The compounds of this invention are administered at a therapeutically effective dosage, i.e., that amount which, when administered to a mammal in need thereof, is sufficient to effect treatment, as described above (for example, to reduce or otherwise treat inflammation, pain and/or pyrexia in the mammal) . Administration of the active compounds and salts described herein can be via any of the accepted modes of administration for agents that serve similar utilities. The level of the drug in a formulation can vary within the full range employed by those skilled in the art, e.g., from about 0.01 percent weight (%w) to about 99.99%w of the drug baεed on the total formulation and about .01%w to 99.99%w excipient. Preferably the drug iε preεent at a level of about 10%w to about 70%w. Generally, an acceptable daily dose is of about 0.001 to 50 mg per kilogram body weight of the recipient per day, preferably about 0.05 to 25 mg per kilogram body weight per day, and most preferably about 0.01 to 10 mg per kilogram body weight per day. Thuε, for administration to a 70 kg person, the dosage range would be about 0.07 mg to 3.5 g per day, preferably about 3.5mg to 1.75 g per day, and most preferably about 0.7 mg to 0.7 g per day depending upon the individuals and disease state being treated. Such use optimization is well within the ambit of those of ordinary skill in the art. Administration can be via any accepted systemic or local route, for example, via parenteral, oral (particularly for infant formulations) , intravenous, nasal, bronchial inhalation (i.e., aerosol formulation), transdermal or topical routes, in the form of solid, semi-solid or liquid dosage forms, such aε for example, tabletε, suppositories, pills, capsules, powders, solutions, suspensions, aerosols, emulεionε or the like, preferably in unit dosage forms εuitable for simple administration of precise dosages. The compositions will include a conventional pharmaceutical carrier or excipient and an active compound of Formula I and, in addition, may include other medicinal agents, pharmaceutical agents, carriers, adjuvants, etc. Carriers can be selected from the various oils, including those of petroleum, animal, vegetable or synthetic origin, for example, peanut oil, soybean oil, mineral oil, εeεame oil, and the like. Water, εaline, aqueouε dextroεe, and glycolε are preferred liquid carrierε, particularly for injectable solutions. Suitable pharmaceutical carriers include starch, cellulose, talc, glucoεe, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, magnesium stearate, sodium εtearate, glycerol monoεtearate, εodium chloride, dried skim milk, glycerol, propylene glycol, water, ethanol, and the like. Other suitable pharmaceutical carriers and their formulations are described in "Remington's Pharmaceutical Sciences" by E. W. Martin. If desired, the pharmaceutical compoεition to be adminiεtered may also contain minor amounts of non-toxic auxiliary substances such as wetting or emulsifying agents, pH buffering agents and the like, εuch as for example, εodium acetate, sorbitan monolaurate, triethanolamine oleate, etc. The compounds of this invention are generally administered as a pharmaceutical composition which comprises a pharmaceutical excipient in combination with a compound of Formula I. The level of the drug in a formulation can vary within the full range employed by those skilled in the art, e.g., from about .01 percent weight (%w) to about 99.99%w of the drug based on the total formulation and about .01%w to 99.99%w excipient. Preferably, the formulation will be about 3.5 to 60% by weight of the pharmaceutically active compound, with the rest being suitable pharmaceutical excipients. INTRAVENOUS ADMINISTRATION Intravenous injection has proven to be an important route of administration for therapeutic agents. The compounds of the present invention can be administered via thiε route, for example, by diεεolving the compound, eεter, ether, N-oxide or εalt in a εuitable εolvent (εuch as water or saline) or incorporation in a liposomal formulation followed, by disperεal into an acceptable infusion fluid. A typical daily dose of a compound of the invention can be administered by one infusion, or by a series of infusions spaced over periodic intervals. ORAL ADMINISTRATION Oral administration can be used to deliver the compound of Formula I using a convenient daily dosage regimen which can be adjusted according to the degree of affliction or for renal impairment, or to compensate for the toxic effects of other medications administered contemporaneously. For such oral adminiεtration, a pharmaceutically acceptable, non-toxic compoεition is formed by the incorporation of any of the normally employed excipients, such aε, for example, pharmaceutical gradeε of mannitol, lactoεe, starch, magnesium stearate, sodium εaccharine, talcum, celluloεe, glucose, gelatin, sucrose, magnesium carbonate, and the like. Such compositions take the form of solutions, suspensions, tablets, pills, capsules, powders, εuεtained releaεe formulations and the like. Such compositionε may contain between .01 wt/wt% and 99.99 wt/wt% of the compound of Formula I, but preferably εuch compoεitionε will contain between 25 wt/wt% and about 80 wt/wt%. Preferably the compoεitions will take the form of a capεule, pill or tablet and thuε the composition will contain, along with the active ingredient, a diluent such aε lactoεe, sucrose, dicalcium phosphate, and the like; a disintegrant εuch aε starch or derivatives thereof; a lubricant such aε magnesium stearate and the like; and a binder such aε a starch, polyvinylpyrrolidone, gum acacia, gelatin, cellulose and derivatives thereof, and the like. For oral administration to infants, a liquid formulation (such aε a εyrup or εuεpenεion) iε preferred. AEROSOL ADMINISTRATION Aeroεol adminiεtration iε an effective means for delivering a therapeutic agent directly to the respiratory tract. Some of the advantages of this method are: 1) it circumvents the effects of enzymatic degradation, poor absorption from the gastrointestinal tract, or loss of the therapeutic agent to the hepatic first-pass effect; 2) it administerε therapeutic agentε which would otherwise fail to reach their target siteε in the reεpiratory tract due to their molecular εize, charge or affinity to extra-pulmonary εiteε; 3) it provides for fast absorption into the body via the alveoli of the lungs; and 4) it avoids exposing other organ systems to the therapeutic agent, which is important where exposure might cause undesirable side effects. For these reasons, aerosol administration iε particularly advantageous for treatment of asthma, local infections of the lung, and other diseaεeε or diεease conditions of the lung and respiratory tract. There are three types of pharmaceutical inhalation devices, nebulizerε inhalerε, metered-dose inhalers (MDI) and dry powder inhalers (DPI) . Nebulizer devices produce a stream of high velocity air that causes the therapeutic agent (which haε been formulated in a liquid form) to εpray as a mist which is carried into the patient's respiratory tract. MDIs typically have the formulation packaged with a compresεed gas. Upon actuation, the device discharges a measured amount of therapeutic agent by compressed gas, thus affording a reliable method of administering a set amount of agent. DPIs administer therapeutic agent ' s in the form of a free flowing powder that can be disperεed in the patient's inspiratory air-stream during breathing by the device. In order to achieve a free flowing powder, the therapeutic agent iε formulated with an excipient, such as lactose. A meaεured amount of the therapeutic agent iε εtored in a capεule form and iε diεpenεed with each actuation. Exampleε of DPIε being uεed are Spinhaler * (for the administration of disodium cromoglycate) , Rotahaler * (for albuterol) and Turbuhaler * (for terbutaline εulfate) . All of the above methods can be used for administering the present invention, particularly for the treatment of asthma and other similar or related respiratory tract disorders. LIPOSOMAL FORMULATIONS Pharmaceutical formulations baεed on liposomes have recently reached human clinical trials. Their benefits are believed related to favorable changes in tiεεue distribution and pharmacokinetic parameters that reεult from liposome entrapment of drugs, and may be applied to the compounds of the present invention by those skilled in the art. The formulations can be designed to either target drug to diεeaεe εites [see: Lopez-Bereεtein et al. , J. Infect . Dis. , 151 : 704-710 (1985); Gotfredsen et al. , Biochemical Pharmacology, 32 : 3389-3396 (1983)]; or to the reticuloendothelial εyεtem [see Eppεtein et al. , Int . J. Immunotherapy , 2 : 115-126 (1986)], to increase duration of drug action [see: Gabizon et al., Cancer Res. , 42 : 4734 (1982); Eppεtein et al., Delivery Systems for Peptide Drugs, Edε. S.S. Daviε, L. Ilium and E. Tomlinεon, Plenum Pub. Corp., New York, pp. 277-283; CA. Hunt, Biochemica et Biophysica Acta . , 719 : 450-463 (1982) ; and Senior et al. , Biochemica et Biophysica Acta . , 839 : 1-8 (1985)] , or to divert a drug away from organε that are particularly εenεitive to its toxic effects [see: Weinstein et al. , Pharmac. Ther . , 24 : 207-233 (1983) ; Olεon et al. , Eur. J. Cancer Clin . Oncol . , 18 : 167-176 (1982); and Gabzion et al. , supra.] . Controlled releaεe lipoεomal liquid pharmaceutical formulations for injection or oral administration are described in U.S. Patent No. 4,016,100. Lipoεomal applications for oral drug delivery of a lyophilized liposome/peptide drug mixture filled into intestine capsules have also been suggeεted, see U.S. Patent No. 4,348,384. SUPPOSITORIES For εystemic adminiεtration via suppository, traditional binders and carriers include, for example, polyalkaline glycol or triglycerides [e.g., PEG 1000 (96%) and PEG 4000 (4%)] . Such suppositories may be formed from mixtures containing active ingredients in the range of from about 0.5 wt/wt% to about 10 wt/wt%; preferably from about 1 wt/wt% to about 2 wt/wt%. LIQUIDS Liquid pharmaceutically administrable compositions can, for example, be prepared by disεolving, disperεing, etc. an active compound (about 0.5% to about 20%) , aε described above, and optional pharmaceutical adjuvantε in a carrier, εuch aε, for example, water, εaline, aqueouε dextroεe, glycerol, ethanol and the like, to thereby form a εolution or suspension. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington 's Pharmaceutical Sciences, Mack Publishing Company, Eaεton, Pennsylvania, 16th Ed., 1980. The composition to be administered will, in any event, contain a quantity of the active compound(ε) in a pharmaceutically effective amount for relief of the particular condition being treated in accordance with the teachings of this invention. EXAMPLES The following examples are given to enable those skilled in the art to more clearly understand and to practice the present invention. They should not be considered as limiting the scope of the invention, but merely as being illustrative and representative thereof. EXAMPLE 1 PREPARATION OF 4- (4-AMINOBENZYL)PYRIDINE 1A. Formula 2, Where R 1 is -Pyridylmethyl 4- (4-Nitrobenzyl)pyridine (214.22 mg) was combined with absolute ethanol (10 mL) and SnCl 2 -2H 2 0 (225.63 mg) . The reaction mixture was heated to 70°C under nitrogen for 2 hours. The progress of the reaction was monitored by thin-layer chromatography (e.g., an aliquot of the mixture was collected, neutralized with saturated NaHC0 3 to pH 7-8, extracted into ethyl acetate) . When all of the starting material had been converted, the reaction mixture was allowed to cool to room temperature, neutralized with saturated NaHC0 3 to pH 7-8 and extracted with ethyl acetate. The organic layers were collected and dried over MgS0 4 . The solvents were removed and the residue was triturated with ethyl ether. The desired product, i.e., 4- (4-aminobenzyl)pyridine, was filtered out of the εolution aε cream colored crystalε and air dried, mp 159.1°C - 160.3°C; elemental analyεis: [calc(found)] C: 78.2 (78.12), H: 6.56 (6.45), and N: 15.20 (15.33) . IB. Compounds of Formula 2, Where R 1 Is Varied Other desired compounds of Formula 2 can be prepared by following the procedures described in Example 1A, and using different starting compounds. For example: 4-isopropylnitrobenzene, 4-methylnitrobenzene, 4- benzylnitrobenzene, 4-ethylnitrobenzene, 4- (3-propenyl)nitrobenzene, 4- propylnitrobenzene, 4-butylnitrobenzene, 4-pentylnitrobenzene, 4-hexylnitrobenzene, 4-methoxynitrobenzene, 4-ethoxynitrobenzene, 4- (trifluoromethyl)nitrobenzene, 4- (3-pyridylmethyl)nitrobenze, 4- (2-pyridylmethyl)nitrobenzene, 4- (cyclopentylmethyl) itrobenzene, 4- (cyclopropylmethyl)nitrobenzene, 4- (thiomethyl)nitrobenzene, and 4- (methylsulfonylmethyl)nitrobenzene can be converted to the corresponding (substituted) anilines. EXAMPLE 2 PREPARATION OF 4- (4-AMINO-3-BROMOBENZYL)PYRIDINE 2A. Formula 3, Where R 1 is 4-Pyridylmethyl A εolution of N-bromoεuccinimide (1.4 gm) in 10 mL dimethylformamide waε added in a dropwise manner to a solution of 4- (4-aminobenzyl)pyridine (1.5 gm) in 10 mL of dimethylformamide. The reaction flask waε wrapped in aluminum foil to prevent expoεure of the reagentε to light. The reaction mixture waε εtirred at room temperature for 3 hourε. The progreεε of the reaction waε monitored by thin-layer chromatography. When the reaction waε completed, the reaction mixture waε combined with 100 mL of H j O with εtirring. A reddiεh brown precipitate waε formed, filtered out of solution, washed with H 2 0, and air dried. The solid waε diεεolved in ethyl acetate, back washed with saturated NaCl, dried over MgS0 4 and triturated with ethyl ether. The solid waε filtered from the solution and air dried yielding 1.6 gm of 4- (4-amino-3-bromobenzyl)pyridine as reddish/tan crystals, mp 102.7°C-103.9°C; 2B. Other Prepared Compounds of Formula 3, Where R 1 Is Varied Other compounds of Formula 3 were alεo prepared following the procedures described in Example 2A, and εubεtituting 4- (4-aminobenzyl) - pyridine with different starting compoundε. For example, following iε a list of starting compounds and the correεponding desired compounds that were obtained by following the above-referenced procedure: 4-isopropylaniline was converted to 2-bromo-4-isopropylaniline, 4-methylaniline waε converted to 2-bromo-4-methylaniline, 4-benzylaniline waε converted to 4-benzyl-2-bromoaniline, and 4- (4-pyridylmethyl)aniline waε converted to 2-bromo-4- (4- pyridylmethyl) aniline. 2C. Compounds of Formula 3, Where R' Is Varied In addition, other deεired compoundε of Formula 3 can be prepared by following the procedureε described in Example 2A, and using different starting compounds. For example, 4-ethylaniline, 4- (3-propenyl)aniline, 4-propylaniline, 4-butylaniline, 4-pentylaniline, 4-hexylaniline, 4-trifluoromethylaniline, 4- (3-pyridylmethyl)aniline, 4- (2-pyridylmethyl)aniline, 4- (cyclopentylmethyl)aniline, 4- (cyclopropylmethyl)aniline, 4- (methylthiomethyl)aniline, and 4- (methylsulfonylmethyl)aniline can be converted to the corresponding 2-bromo-4- (substituted) -anilines. EXAMPLE 3 PREPARATION OF 3-CHLOROBENZENE BORONIC ACID 3A. Formula 3B Where R 2 is 3-chlorophenyl A solution of trimethylborate in 200 mL of ethyl acetate was cooled to -65°C 3-Chlorobenzene magneεium chloride (0.8 M, 60 mL) , i.e., a Grignard reagent, was added to the εolution in a dropwise manner over 20 minutes. The mixture was kept in the temperature range of -60°C to -70°C and stirred. After 30 minuteε, the mixture was allowed to warm to 0°C and stirred for 1 hour. The mixture waε quenched with H 2 0 (25 mL) and εtirred at room temperature for 1 hour. The εolvent waε removed and the remaining maεε waε extracted with ethyl ether (3 x 100 mL) . The organic layerε were combined and washed with H 2 0 (2 x 50 mL) , dilute HCl (2 x 100 mL) , H 2 0 (2 x 50 mL) and brine (1 x 50 mL) . The organic layer was dried over MgS0 4 , concentrated and allowed to εtand. 100 mL of hexaneε was added and the solution was εtirred for 1 hour. The εolution waε filtered and allowed to air dry yielding 4.6 g of 3-chlorobenzene boronic acid aε a white solid. 3B. Compounds of Formula 3B where R 2 is optionally substituted Other desired compounds of Formula 3B can be prepared by following the procedures described in Example 3A, and using different starting compounds. For example, 3-chloro-4-fluorobenzene magnesium chloride, 4- chlorobenzene magnesium chloride, benzene magnesium bromide, 3,4- dichlorobenzene magnesium bromide, 3-bromobenzene magneεium bromide, and 3- (trifluoromethyl)benzene magneεium bromide can be converted to the correεponding (substituted) benzene boronic acidε. EXAMPLE 4 PREPARATION OF 4- [4-AMINO-3- (3-NITROPHENYL) - BENZYL]PYRIDINE 4A. Formula 4, Where R 1 is -Pyridylmethyl, R 2 is 3-Nitrophenyl. 4- (4-Amino-3-bromobenzyl)pyridine (1.0 gm) , 3-nitrobenzene boronic acid (0.63 gm) , palladium tetrakiε triphenylphoεphine (0.47 gm) , methanol (6.5 mL) , 2.0 M Na 2 C0 3 (1.9 mL) and benzene (32 mL) were combined in a reaction flask that waε wrapped in aluminum foil (to prevent exposure of the reagents to light) . The reaction mixture was heated under reflux for 6 hours. The progress of the reaction was monitored by thin-layer chromatography (9:1 hexane:ethyl acetate). When the εtarting material was converted, the reaction mixture was allowed to cool and the solvents were removed. Ethyl acetate was added to the reεidue, the reεultant εolution was filtered through a pad of Na 2 S0 4 , and concentrated. The product was isolated by preparative thin-layer chromatography (9:1 hexane:ethyl acetate) yielding 983 mg of 4- [4-amino-3- (3-nitrophenyl)benzyl]pyridine as an orange oil. Characteristic analytical data: ms m/e 305 (M+) ; ! H NMR (CDC1 3 ) δ 3.74 (bs, 2H) , 3.92 (s, 2H) , 6.77 (d, 1H, J=8.1 Hz), 6.95 (d, 1H, J=2.1 Hz), 7.03 (dd, 1H, J=2.1 Hz, J=8.1 Hz), 7.14 (d, 1H, J=5.7 Hz), 7.62 (dd, 1H, J=8.2 Hz, J=7.7 Hz), 7.82 (ddd, 1H, J=7.7 Hz, J=1.9 Hz, J=2.5Hz), 8.21 (ddd, 1H, J=8.2 Hz, J=2.5 Hz, J=1.9Hz), 8.34 (dd, 1H, J=1.9 Hz, J=1.9 Hz), and 8.5 (dd, 1H, J=5.7 Hz). 4B. Other Compounds of Formula 4, Where R 1 and R 2 Are Varied. Other compounds of Formula 4 were also prepared following the procedures described in Example 4A, and subεtituting for 4- (4-amino-3- bromobenzyl)pyridine and 3-nitrobenzene boronic acid with different εtarting compoundε. For example, following iε a liεt of εtarting compoundε and the correεponding deεired compoundε that were obtained by following the above-referenced procedure: 2-bromo-4-iεopropylaniline and benzene boronic acid were combined to form 2-phenyl-4-iεopropylaniline, 2-bromo-4-iεopropylaniline and 3-nitrobenzene boronic acid were combined to form 2- (3-nitrophenyl) -4-iεopropylaniline, 4-benzyl-2-bromo-aniline and 3-nitrobenzene boronic acid were combined to form 4-benzyl-2- (3-nitrophenyl) -aniline, 2-bromo-4-methylaniline and 3-chloro-4-fluorobenzene boronic acid were combined to form 2- (3-chloro-4-fluorophenyl) -4- methylaniline, 2-bromo-4-iεopropylaniline and 3-chloro-4-fluorobenzene boronic acid were combined to form 2- (3-chloro-4-fluorophenyl) -4- iεopropylaniline, 4-benzyl-2-bromo-aniline and 3-chloro-4-fluorobenzene boronic acid were combined to form 4-benzyl-2- (3-chloro- -fluorophenyl) - aniline, 2-bromo-4- (4-pyridylmethyl)aniline and 3-chloro-4-fluorobenzene boronic acid were combined to form 2- (3-chloro-4-fluorophenyl) - 4- (4-pyridylmethyl)aniline, 2-bromo-4-methylaniline and 4-chlorobenzene boronic acid were combined to form 2- (4-chlorophenyl) -4-methylaniline, 2-bromo-4-isopropylaniline and 4-chlorobenzene boronic acid were combined to form 2- (4-chlorophenyl) -4-iεopropyl aniline, and 2-bromo-4-benzylaniline and -chlorobenzene boronic acid were combined to form 2- (4-chlorophenyl) -4-benzyl- aniline. 4C. Compounds of Formula 4, Where R 1 and R 2 Are Varied In addition, other desired compounds of Formula 4 can be prepared by following the procedureε deεcribed in Example 4A, and uεing different starting compoundε. For example, 2-bromo-4-ethylaniline and 3- (trifluoromethyl)benzene boronic acid can be combined to form 2- (3-trifluoromethylphenyl) -4- ethylaniline, 2-bromo-4-iεopropylaniline and 3,4-dichlorobenzene boronic acid can be combined to form 2- (3,4-dichlorophenyl) -4-iεopropylaniline, 2-bromo-4- (3-propenyl)aniline and 3-nitrobenzene boronic acid can be combined to form 2- (3-nitrophenyl) -3-properylaniline, 2-bromo-4-propylaniline and 3-nitrobenzene boronic acid can be combined to form 2- (3-nitrophenyl) -4-propylaniline, 2-bromo-4- (n-butyl)aniline and 3-nitrobenzene boronic acid can be combined to form 2- (3-nitrophenyl) -4- (n-butyl)aniline, 2-bromo-4- (n-hexyl)aniline and benzene boronic acid can be combined to form 2-phenyl-4- (n-hexyl)aniline, 2-bromo-4-pentylaniline and 3-nitrobenzene boronic acid can be combined to form 2- (3-nitrophenyl) -4-pentylaniline, 2-bromo-4-benzylaniline and 3,4-dichlorobenzene boronic acid can be combined to form 2- (3,4-dichlorophenyl) -4-benzylaniline, 2-bromo-4-cyclopentylmethylaniline and 3-chlorobenzene boronic acid can be combined to form 2- (3-chlorophenyl) -4- cyclopentylmethylaniline, 2-bromo-4-cyclopropylmethylaniline and 3-nitrobenzene boronic acid can be combined to form 2-bromo-4-cyclopropyl- methylaniline, 2-bromo-4- (methylthiomethyl)aniline and 3-chlorobenzene boronic acid can be combined to form 2- (3-chlorophenyl) -4- (methylthiomethyl)aniline, 2-bromo-4- (methylεulfonylmethyl)aniline and benzene boronic acid can be combined to form 2-phenyl-4- (methylεulfonyl- methyl)aniline, 2-bromo-4- (cyclopentylmethyl)aniline and 2,3-dichlorobenzene boronic acid can be combined to form 2- (2,3-dichlorophenyl) -4- (cyclopentylmethyl)aniline, and 2-bromo-4- (cyclopentylmethyl)aniline and 3-nitrobenzene boronic acid can be combined to form 2- (3-nitrophenyl) -4- (cyclopentylmethyl)aniline. EXAMPLE 5 PREPARATION OF 6- (4-PYRIDYLMETHYL) -8- (3-NITROPHENYL)QUINOLINE 5A. Formula I, Where R 1 is 4-Pyridylmethyl, R 2 is 3-Nitrophenyl. 4- [4-Amino-3- (3-nitrophenyl)benzyl]pyridine (600 mg) was combined with glycerol (489 mg) and arsenic pentoxide (325 mg) under nitrogen. The reaction mixture was heated to 100°C for 30 minutes. Concentrated sulfuric acid (406 mg) waε added in a dropwise manner and the reaction mixture was further heated to 150°C for 2 hours. The reaction was monitored by TLC (9:1, hexane:ethyl acetate) . When TLC indicated that greater than 90% of the starting material had been converted, the reaction mixture was removed from the heat, ice (approximately 1 gm) was added, and NH 4 OH was added to basify the mixture. A precipitate was filtered out of the mixture, waεhed with H 2 0 and air dried. The resulting solid waε suspended in hot ethyl acetate and filtered. The filtrate was concentrated and chromatographed by preparative thin-layer chromatography (4:1, hexane:ethyl acetate), the band with the higher R f value was isolated yielding 181 mg of 6- (4-pyridylmethyl) -8- (3- nitrophenyl)quinoline as a viscous yellow oil. The product was recryεtallized from diethyl ether as a light yellow solid. Characteristic analytical data: mp 131°C-143°C; elemental analysiε, calc(found) C: 73.89 (73.90), H: 4.43 (4.50), and N: 12.31 (12.30); Η NMR CDC1 3 δ 4.21 (s, 2H) , 7.21 (d, 2H, J=5.9 Hz), 7.48 (dd, 1H, J=8.3 Hz, J=4.2 Hz), 7.6 (d, 1H, J=2 Hz), 7.66 (dd, 1H, J=8 Hz, J=7.7 Hz), 7.7 (d, 1H, J=2Hz) , 8.03 (ddd, 1H, J=7.7 Hz, J=1.4 Hz, J=1.2 Hz), 8.2 (dd, 1H, J=8.3 Hz, J=1.7 Hz, J=1.2 Hz), 8.28 (ddd, 1H J=8 Hz, J=1.44 Hz, J=1.2 Hz), 8.55 (m, 3H) , 8.93 (dd, 1H, J=4.2 Hz, J=l.7 Hz). 5B. Other Compounds of Formula I, Where R 1 and R 2 Are Varied. Other compounds of Formula I were also prepared following the procedures described in Example 5A, and εubstituting 4- [4-amino-3- (3- nitrophenyl)benzyl]pyridine with different εtarting compoundε. For example, following iε a liεt of starting compounds and the corresponding deεired compounds that were obtained by following the above-referenced procedure: 2-phenyl-4-isopropylaniline waε converted to 6-isopropyl-8- phenylquinoline as an oil, 2- (3-nitrophenyl) -4-iεopropylaniline was converted to 6-isopropyl-8- (3-nitrophenyl)quinoline as an oil, 4-benzyl-2- (3-nitrophenyl)aniline was converted to 6-benzyl-8- (3- nitrophenyl)quinoline, mp 101°C-103°C, 2- (3-chloro-4-fluorophenyl) -4-methylaniline was converted to 6- methyl-8- (3-chloro-4-fluorophenyl)quinoline, mp 96°C-114°C, 2- (3-chloro-4-fluoro) -4-iεopropylaniline was converted to 6-isopropyl-8- (3-chloro-4-flue . τyl)quinoline as an oil, 4-benzyl-2- (3-chloro-4-fluoro ^aniline was converted to 6- benzyl-8- (3-chloro-4-flut j.enyl)quinoline as an oil, 2- (3-chloro-4-fluorophenyl) -4- (4-pyridylmethyl)aniline waε converted to 6- (4-pyridylmethyl) -8- (3-chloro-4-fluorophenyl)quinoline as an oil, 2- (4-chlorophenyl) -4-methylaniline was converted to 6-methyl-8- (4- chlorophenyl)quinoline, mp 96°C-98°C, 2- (4-chlorophenyl) -4-isopropylaniline was converted to 6-isopropyl-8- (4-chlorophenyl)quinoline as an oil, and -benzyl-2- (4-chlorophenyl)aniline was converted to 6-benzyl-8- (4- chlorophenyl)quinoline as an oil. 5C. Formula I, Where R 1 and R 2 Are Varied In addition, other deεired compounds of Formula I can be prepared by following the procedures described in Example 5A, and using different starting compounds. For example, 2- (3-trifluoromethylphenyl) -4-ethylaniline can be converted to 6-ethyl-8- (3-trifluoromethylphenyl)quinoline, 2- (3,4-dichlorophenyl) -4-isopropylaniline can be converted to 6-isopropyl-8- (3,4-dichlorophenyl)quinoline, 2- (3-nitrophenyl) -4- (3-propenyl)aniline can be converted to 6- (3-propenyl) -8- (3-nitrophenyl)quinoline, 2- (3-nitrophenyl) -4-propylaniline can be converted to 6-propyl-8- (3-nitrophenyl)quinoline, 2- (3-nitrophenyl) -4-butylaniline can be converted to 6-butyl-8- (3-nitrophenyl)quinoline, 2- (phenyl) -4-hexylaniline can be converted to 6-hexyl-8- (phenyl)quinoline, 2- (3-nitrophenyl) -4-pentylaniline can be converted to 6-pentyl-8- (3-nitrophenyl)quinoline, 2- (3,4-dichlorophenyl) -4-benzylaniline can be converted to 6-benzyl-8- (3,4-dichlorophenyl)quinoline, 2- (3-methoxycarbonylphenyl) -4- (3-pyridylmethyl)aniline can be converted to 6- (3-pyridylmethyl) -8- (3-methoxycarbonylphenyl) - quinoline, 2- (3-methoxycarbonylphenyl) -4- (2-pyridylmethyl)aniline can be converted to 6- (2-pyridylmethyl) -8- (3-methoxycarbonylphenyl) - quinoline, 2- (3-chlorophenyl) -6-cyclopentylmethylaniline can be converted to 6- cyclopentylmethyl-8- (3-chlorophenyl)quinoline, 2- (3-nitrophenyl) -4-cyclopropylmethylaniline can be converted to 6- cyclopropylmethyl-8- (3-nitrophenyl)quinoline, 2- (3-chlorophenyl) -4- (methylthiomethyl)aniline can be converted to 6- methylthiomethyl-8- (3-chlorophenyl)quinoline, 2-phenyl-4- (methylεulfonylmethyl)aniline can be converted to 6- ethylεulfonylmethyl-8- (phenyl)quinoline, 2- (3,4-dichlorophenyl) -4- (cyclopentylmethyl)aniline can be converted to 6-cyclopentylmethyl-8- (3,4-dichlorophenyl) quinoline, and 2- (3-nitrophenyl) -4- (cyclohexylmethyl)aniline can be converted to 6- cyclohexylmethyl-8- (3-nitrophenyl)quinoline. EXAMPLE 6 PREPARATION OF 6-ISOPROPYL-8-BROMOQUINOLINE 6A. Formula 5 Where R 1 Is Isopropyl 2-Bromo-4-isopropylaniline (3.0 gm) [obtained from Aldrich Chemical Co.], glycerol (2.8 Ml) and arsenic pentoxide (3.22 g) were combined and heated to 100°C H 2 S0 4 (concentrated, 1.9 Ml) was added to the reaction mixture in a dropwise manner. The mixture was then heated to 150°C for 2.5 hours. The resulting black oil waε added in a dropwiεe manner to a εtirring mixture of εaturated NaHC0 3 (300 Ml) and ethyl acetate (100 Ml) . After completion of the addition, the reaction mixture was εtirred for 30 minuteε. The reaction mixture waε then extracted with ethyl acetate (2 x 200 Ml) . The organic layerε were washed with brine, dried over MgS0 4 , filtered and concentrated. The resulting material was further purified and isolated by chromatography on silica gel (30:70 ethyl acetate/hexanes) which yielded 2.5 g of 6-isopropyl-8-bromoquinoline aε a brown oil. Characteriεtic analytical data: elemental analyεiε calc. (found) : C 57.62 (57.65), H 4.84 (4.78), and N 5.60 (5.57) ; Η NMR (CDC1 3 ) δ 1.34 (d, 6H, J=6.9 Hz), 3.05 (m, 1H, J=6.9 Hz), 7.42 ( (dd, 1H, J=4.2 Hz, J=8.3 Hz) , 7.57 (d, 1H, J=1.8 Hz), 7.97 (d, 1H, J=1.8 Hz), 8.1 (dd, 1H, J=8.3 Hz, J=1.7 Hz), and 8.9 (dd, 1H, J=4.2 Hz, J=1.7 Hz) . EXAMPLE 7 PREPARATION OF 6-ISOPROPYL- 8- (3-NITROPHENYL)QUINOLINE HYDROCHLORIDE 7A. Formula I Where R 1 Is Isopropyl and R 2 Is 3-Nitrophβnyl. 6-Iεopropyl-8-bromoquinoline (1.15 g) waε diεεolved in 46 Ml of ethanol/benzene (1:1) . 3-Nitrobenzene boronic acid (1.4 g) , Na 2 C0 3 (2M, 9.2 Ml) and tetrakiε (triphenylphosphine)palladium (0.23 g) were added εuccessively. The reaction mixture waε refluxed for 6 hours and then cooled and concentrated. The resulting residue was partitioned between 75 mL H 2 0 and 100 mL of ethyl acetate, and extracted with ethyl acetate (2 x 100 mL) . The extracts were then dried over MgS0 4 , filtered, concentrated and chromatographed on εilica gel (20:80 ethyl acetate:hexane) yielding 1.2 g of 6-isopropyl-8- (3-nitrophenyl) - quinoline as a εlightly impure yellow oil. The desired product was obtained in its pure form by recrystallization of its hydrochloride salt. The oil was dissolved in 25 mL of 10% methanol:methylene chloride, to which a solution of 1M HCl/Et 2 0 (100 mL) was added. The solution waε εtirred for 10 minuteε and then concentrated. The resulting white solid waε recrystallized from ethyl acetate:ethanol yielding 0.74 g of 6-iεopropyl-θ- (3-nitrophenyl)quinoline aε pale yellow cryεtalε. Characteriεtic analytical data: elem. anal. calc. (found) : C 65.75 (65.92), H 5.21 (5.21), and N 8.52 (8.67); and Η NMR (DMSO) δ 1.37 (d, 6H, J=6.9 Hz), 3.2 (m, 1H, J=6.9 Hz), 7.81 (m, 2H) , 7.92 (d, 1H, J=1.9 Hz), 8.09 (d, 1H, J=1.9 Hz), 8.11 (m, 1H) , 8.43 (m, 1H) , 8.53 (m, 1H) , 8.7 (dd, 1H, J=1.5 Hz, J=8.3 Hz), 8.9 (dd, 1H, <J=4.7 Hz, J=8.3 Hz) . EXAMPLE 8 PREPARATION OF 6-METHYL-8-BROMOQUINOLINE 8A. Formula 5 Where R 1 is Methyl and X is Bromo A εlurry of 2-bromo-4-methylaniline (5 g) , glycerol (6.7 g) , and arεenic pentoxide (3.9 g) waε formed and heated to 100°C for 30 minuteε. Concentrated HjSO,, (4.9 g) was added dropwise and the mixture was heated to 150°C for two hours. The progress of the reaction waε monitored by thin-layer chromatography (9:1 hexane:ethyl acetate) . Upon completion, the reaction mixture waε worked up by adding water, baεifying with εaturated NaHC0 3 , extracting with ethyl acetate, and drying the organic layer over MgS0 4 . The deεired product waε iεolated and purified by column chromatography (9:1 hexane:ethyl acetate), yielding 6-methyl-8- bromoquinoline (1.8 g) aε a yellow liquid. Characteriεtic analytical data: l H NMR (CDC1 3 ) δ 2.5 (ε, 3H) , 7.4 (dd, 1H, J=8.3 Hz, J=4.3 Hz), 7.52 (bs, 1H) , 7.9 (d, 1H, J=1.8 Hz), 8.07 (dd, 1H, J=8.3 Hz, J=1.7 Hz), 8.88 (dd, 1H, J=4.3 Hz, J=l.7 Hz) . 8B. Formula 5 Where R 1 Is Varied Following the procedures deεcribed in Example 8A the following deεired compounds of Formula 5 can be obtained from the indicated starting compounds. For example, 2-bromo-4-isopropylaniline and glycerol can be combined to form 6- iεopropyl-8-bromoquinoline, 2-bromo-4-methylaniline and glycerol can be combined to form 6-methyl-8-bromoquinoline, 2-bromo-4-benzylaniline and glycerol can be combined to form 6-benzyl-8-bromoquinoline, 2-bromo-4- (4-pyridylmethyl)aniline and glycerol can be combined to form 6- (4-pyridylmethyl) -8-bromoquinoline, 2-bromo-4-ethylaniline and glycerol can be combined to form 6-ethyl-8-bromoquinoline, 2-bromo-4- (3-propenyl)aniline and glycerol can be combined to form 6- (3-propenyl) -8-bromoquinoline, 2-bromo-4-propylaniline and glycerol can be combined to form 6-propyl-8-bromoquinoline, 2-bromo-4- (n-butyl) aniline and glycerol can be combined to form 6- (n- butyl) -8-bromoquinoline, 2-bromo-4-pentylaniline and glycerol can be combined to form 6-pentyl-8-bromoquinoline, 2-bromo-4-hexylaniline and glycerol can be combined to form 6-hexyl-8-bromoquinoline, 2-bromo-4- (3-pyridylmethyl)aniline and glycerol can be combined to form 6- (3-pyridylmethyl) -8-bromoquinoline, 2-bromo-4- (2-pyridylmethyl)aniline and glycerol can be combined to form 6- (2-pyridylmethyl) -8-bromoquinoline, 2-bromo-4- (cyclopentylmethyl)aniline and glycerol can be combined to form 6- (cyclopentylmethyl) -8-bromoquinoline, 2-bromo-4- (eyelopropylmethy1)aniline and glycerol can be combined to form 6- (cyclopropylmethyl) -8-bromoquinoline, 2-bromo-4- (methylthiomethyl)aniline and glycerol can be combined to form 6- (methylthiomethyl) -8-bromoquinoline, and 2-bromo-4- (methylsulfonylmethyl)aniline and glycerol can be combined to form 6- (methylsulfonylmethyl) -8-bromoquinoline. EXAMPLE 9 PREPARATION OF 6-METHYL-8- (3-NITROPHENYL)QUINOLINE 9A. Formula I, Where R 1 is Methyl and R 2 is 3-Nitrophenyl. To a mixture of 6-methyl-8-bromoquinoline (1.0 g) , 3-nitrobenzene boronic acid (0.63 g) , purchaεed from Lancaεter Chemicals, 2M NaC0 3 (1.9 mL) , methanol (6.5 mL) and benzene 32 mL) waε added palladium tetrakiε triphenylphosphine (0.47 g) . The mixture was heated under reflux for 6 hours. The progress of the reaction was monitored by thin-layer chromatography. Upon completion, the reaction mixture was cooled and the solvents removed. Ethyl acetate waε added to the reεidue and the εolution waε filtered through a pad of Na 2 S0 4 . The εolution waε concentrated and the deεired product waε purified and iεolated by preparative thin-layer chromatography yielding 6-methyl-8- (3-nitrophenyl)quinoline (983 mg) aε a yellow oil. Elemental analysis [calc. (found) ] C: 72.72 (72.63), H: 4.58 (4.32), and N: 10.60 (10.72) . 9B. Formula I, Where R 1 and R 2 Are Varied The compoundε of Formula I that were prepared following the procedureε deεcribed in Exampleε 1-5 (i.e., following Reaction Scheme A) can also be prepared by following the procedureε deεcribed in Exampleε 6, 7, 8 and 9 (i.e., following Reaction Scheme B) . For example, 6-isopropyl-8-bromoquinoline combined with benzene boronic acid can be converted to 6-isopropyl-8-phenylquinoline, 6-isopropyl-8-bromoquinoline combined with 3-nitrobenzene boronic acid can be converted to 6-isopropyl-8- (3-nitrophenyl) - quinoline, 6-benzyl-8-bromoquinoline combined with 3-nitrobenzene boronic acid can be converted to 6-benzyl-8- (3-nitrophenyl)quinoline, 6-methyl-8-bromoquinoline combined with 3-chloro-4-fluorobenzene boronic acid can be converted to 6-methyl-8- (3-chloro-4-fluoro¬ phenyl)quinoline, 6-isopropyl-8-bromoquinoline combined with 3-chloro-4-fluoro- benzene boronic acid can be converted to 6-isopropyl-8- (3-chloro-4-fluorophenyl) quinoline, 6-benzyl-8-bromoquinoline combined with 3-chloro-4-fluorobenzene boronic acid can be converted to 6-benzyl-8- (3-chloro-4- fluorophenyl) quinoline, 6- (4-pyridylmethyl) -8-bromoquinoline combined with 3-chloro-4- fluorobenzene boronic acid can be converted to 6- (4- pyridylmethyl) -8- (3-chloro-4-fluorophenyl)quinoline, 6-methyl-8-bromoquinoline combined with 4-chlorobenzene boronic acid can be converted to 6-methyl-8- (4-chlorophenyl) - quinoline, 6-isopropyl-8-bromoquinoline combined with 4-chlorobenzene boronic acid can be converted to 6-isopropyl-8- (4- chlorophenyl)quinoline, and 6-benzyl-8-bromoquinoline combined with 4-chlorobenzene boronic acid can be converted to 6-benzyl-8- (4-chlorophenyl) - quinoline. 9C. Formula I, Where R 1 and R 2 Are Varied In addition, other deεired compoundε of Formula I can be prepared by following the procedureε described in Example 9A, and using different εtarting compounds. For example, 6-ethyl-8-bromoquinoline and 3,4 dichlorobenzene boronic acid can be combined to form 6-ethyl-8- (3,4-dichlorophenyl) quinoline, 6- (3-propenyl) -8-bromoquinoline and 3- (trifluoromethyl)benzene boronic acid can be combined to form 6- (3-propenyl) - 8- (3-trifluoromethylphenyl)quinoline, 6-propyl-8-bromoquinoline and 3-nitrobenzene boronic acid can be combined to form 6-propyl-8- (3-nitrophenyl) quinoline, 6- (n-butyl) -8-bromoquinoline and 3-chlorobenzene boronic acid can be combined to form 6- (n-butyl) -8- (3-chlorophenyl) quinoline, 6-pentyl-8-bromoquinoline and 3,4-dichlorobenzene boronic acid can be combined to form 6-pentyl-8- (3,4-dichlorophenyl) quinoline, 6-hexyl-8-bromoquinoline and 3-nitrobenzene boronic acid can be combined to form 6-hexyl-8- (3-nitrophenyl)quinoline, 6- (3-pyridylmethyl) -8-bromoquinoline and 3-nitrobenzene boronic acid can be combined to form 6- (3-pyridylmethyl) -8- (3-nitrophenyl)quinoline, 6- (2-pyridylmethyl) -8-bromoquinoline and 3-chlorobenzene boronic acid can be combined to form 6- (2-pyridylmethyl) - 8- (3-chlorophenyl) quinoline, 6- (cyclopentylmethyl) -8-bromoquinoline and 3-chloro-4-fluorobenzene boronic acid can be combined to form 6- (cyclopentylmethyl) -8- (3-chloro-4-fluorophenyl)quinoline, 6- (cyclopropylmethyl) -8-bromoquinoline and benzene boronic acid can be combined to form 6- (cyclopropylmethyl) -8-phenyl- quinoline, 6- (methylthiomethyl) -8-bromoquinoline and benzene boronic acid can be combined to form 6- (methylthiomethyl) -8-phenylquinoline, and 6- (methylsulfonylmethyl) -8-bromoquinoline and 3-nitrobenzene boronic acid can be combined to form 6- (methylsulfonyl- methyl) -8- (3- nitrophenyl)quinoline. EXAMPLE 10 PREPARATION OF 8- {3-CHLOROPHENYL) -6-QUINOLINECARBOXALDEHYDE 10A. Formula I Where R 1 is Bromomethyl 6-Methyl-8- (3-chlorophenyl)quinoline (prepared following the procedureε deεcribed in Example 9, Reaction Scheme B) (1.64 g) waε combined with 30 mL of carbon tetrachloride and heated to reflux. N-Bromoεuccinamide (1.34 g) and 2,2 ' -azobiε (2-methylpropionitrile) (0.025 g) waε added and the reaction mixture was exposed to light from a 250 watt light bulb for 1 hour. The reaction mixture waε then stirred for an additional 2 hourε. The progreεε of the reaction waε monitored by thin- layer chromatography (9:1 hexane/ethyl acetate) . Upon completion of the reaction, the reaction mixture waε cooled to 0°C and poured through a 2cm pad of Na 2 S0 4 on 1cm pad on εilica gel. The filtrate waε concentrated yielding 2.26 g of a yellow oil as a mixture of the monobrominated compound as the major product as well as the dibrominated compound aε the minor product. The crude oil (1.84 g) was dissolved in 25 mL of chloroform and added dropwise to a solution of tetra n-butylammonium dichromate (19.4 g) in methylene chloride (30 mL) and refluxed for 4 hourε. The reaction mixture waε then cooled to room temperature, filtered through εilica gel, eluted with ether and concentrated. The reεidue was chromatographed in hexane:ethyl acetate (70:30) to obtain 8- (3-chlorophenyl) -6- quinolinecarboxaldehyde (0.93 g) . Characteristic analytical data: Η NMR (CDC1 3 ) δ 7.41 (m, 2H) 7.52 (dd, 1H, J=5.2 Hz, J=4.2 Hz) , 7.6 (m, 1H) , 7.71 (m, 1H) , 8.19 (d, 1H, J=1.9 Hz) , 8.38 (d, IH, J=1.9 Hz), 8.4 (dd, IH, J=5.2 Hz, J=l.8 Hz), 9.6 (dd, IH, J=4.2 Hz, J=1.8 Hz), 10.22 (ε, IH) ; and elemental analyεis for C 16 H 10 C1NO, calc(found) C, 71.78 (71.79) ; H, 3.77 (3.81); N, 5.23 (5.39) . 10B. Formula I, Where R 1 Is Bromomethyl and R 2 Is Varied. Following the procedures deεcribed in Example 10A the following deεired compoundε of Formula I where R 1 iε bromomethyl can be obtained from the indicated εtarting compoundε. For example, 6-methyl-8- (3-nitrophenyl) quinoline can be converted to 8- (3-nitrophenyl) -6-quinolinecarboxaldehyde, 6-methyl-8-phenylquinoline can be converted to 8-phenyl-6-quinolinecarboxaldehyde, 6-methyl-8- (3-chlorophenyl)quinoline can be converted to 8- (3- chlorophenyl) -6-quinolinecarboxaldehyde, 6-methyl-8- (3-trifluoromethylphenyl)quinoline can be converted to 8- (3-trifluoromethylphenyl) -6-quinolinecarboxaldehyde, 6-methyl-8- (3-chlorophenyl)quinoline can be converted to 8- (3-chlorophenyl) -6-quinolinecarboxaldehyde, 6-methyl-8- (3-chloro-4-fluoro-phenyl) quinoline can be converted to 8- (3-chloro-4-fluorophenyl) -6-quinolinecarboxaldehyde, 6-methyl-8- (3,4-dichlorophenyl)quinoline can be converted to 8- (3,4-dichlorophenyl) -6-quinolinecarboxaldehyde, and 6-methyl-8- (4-chlorophenyl)quinoline can be converted to 8- (4-chlorophenyl) -6-quinolinecarboxaldehyde. EXAMPLE 11 PREPARATION OF 6- (1-HYDROXYETHYL) -8- (3-CHLOROPHENYL)QUINOLINE 11A. Formula I Where R 1 Is 1-hydroxyethyl 8- (3-Chlorophenyl) -6-quinolinecarboxaldehyde (0.8 g) was disεolved in 20 mL of tetrahydrofuran and cooled to -78°C Methyllithium (4.5 mL, 1.4M) in diethyl ether waε added dropwise to the solution over 5 minutes. The solution was stirred for 20 minutes, poured into 50 mL of εaturated ammonium chloride, εtirred for 5 minuteε and extracted with ethyl acetate (2 x 75 m ) . The extracts were combined and dried over MgS0 4 , and concentrated. The residue was chromatographed on εilica gel (30:70 ethyl acetate:hexaneε) to obtain 0.72 g of 6- (1-hydroxyethyl) -8- (3-chlorophenyl) - quinoline as a yellow oil. Characteristic analytical data: Η NMR (CDC1 3 ) δ 1.6 (d, 3H, J=6.5 Hz), 5.1 (q, IH, J=6.5 Hz), 7.4 (m, 3H) , 7.55 (m, IH) , 7.67 (m, IH) , 7.7 (d, IH, J=1.9 Hz), 7.8 (d, IH, J=1.9 Hz), 8.18 (dd, IH, J=8.3 Hz, J=l.8 Hz), 8.9 (dd, IH, J=4.2 Hz, J=1.8 Hz) . 11B. Formula I, Where R 1 Is Formyl and R 2 Is Varied Following the procedures described in Example 11A the following desired compounds of Formula I where R 1 iε formyl can be obtained from the indicated εtarting compounds. For example, 8- (3-nitrophenyl) -6-quinolinecarboxaldehyde and methyllithium can be converted to 6- (1-hydroxyethyl) -8- (3-nitrophenyl) - quinoline, 8-phenyl-6-quinolinecarboxaldehyde and n-butyl magnesium chloride can be converted to 6- (1-hydroxypentyl) -8-phenylquinoline, 8- (3-chlorophenyl) -6-quinolinecarboxaldehyde and ethyllithium can be converted to 6- (1-hydroxypropyl) -8- (3-chlorophenyl) - quinoline, 8- (3-trifluoromethylphenyl) -6-quinolinecarboxaldehyde and hexyl magneεium chloride can be converted to 6- (1-hydroxy- heptyl) -8- (3-trifluoromethylphenyl)quinoline, 8- (3-chlorophenyl) -6-quinolinecarboxaldehyde and methyl magneεium chloride can be converted to 6- (1-hydroxyethyl) -8- (3- chlorophenyl)quinoline, 8- (3-chloro-4-fluorophenyl) -6-quinolinecarboxaldehyde and methyllithium can be converted to 6- (1-hydroxyethyl) -8- (3- chloro-4-fluorophenyl) quinoline, 8- (3,4-dichlorophenyl) -6-quinolinecarboxaldehyde and propyllithium can be converted to 6- (1-hydroxybutyl) -8- (3,4- dichlorophenyl)quinoline, and 8- (4-chlorophenyl) -6-quinolinecarboxaldehyde and hexyllithium can be converted to 6- (1-hydroxyheptyl) -8- (4-chlorophenyl) - quinoline. EXAMPLE 12 PREPARATION OF 6- (4-PYRIDY -N-OXIDE-METHYL) -8- (3-NITROPHENYL)QUINOLINE To a εolution of 6- (4-pyridylmethyl) -8- (3-nitrophenyl)quinoline (100 mg) in methylene chloride (10 mL) under nitrogen at room temperature waε added m-chloroperoxybenzoic acid (59 mg) . The reaction mixture waε εtirred at room temperature for 3~4 hours. The progress of the reaction was monitored by TLC. Upon completion of the reaction, the reaction mixture was worked up by preparative thin-layer chromatography yielding 6- (4- pyridyl-N-oxide-methyl) -8- (3-nitrophenyl)quinoline (87 mg) as creme colored crystals. Characteriεtic analytical data: ! H (CDC1 3 ) δ 4.21 (ε, 2H) , 7.13 (d, 2H, J=5.2 Hz), 7.43 (dd, IH, J=8.2 Hz, J=4.2 Hz), 7.5 (d, IH, J=1.9 Hz), 7.6 (dd, IH, J=8 Hz, J=8 Hz), 7.7 (d, IH, <J=1.9 Hz), 7.95 (ddd, IH J=7.7 Hz, J=1.4 Hz, J=1.3 Hz), 8.13 (d, 2H, J=5.2 Hz), 8.18 (dd, IH, J=8.2 Hz, J=1.7 Hz), 8.?1 (ddd, IH, J=8.2 Hz, J=J.14, J=1.3 Hz), 8.55 (dd, IH, J=1.3 Hz, J=1.3 Hz), 8.92 (dd, IH, J=4.2 Hz, J=1.7 Hz) . EXAMPLE 13 (REACTION SCHEMES B-1, B) PREPARATION OF 6-BROMOMETHYL-8-BROMOQUINO INE Formula 5, Where R 1 Is Bromomethyl and R 2 Is Bromo 3.7g (16.66 mmol) of 6-Methyl-8-bromoquinoline was disεolved in 85mL of CC1 4 and 3g of N-bromoεuccinamide (16.66 mmol) was added followed by a catalytic amount of azobiεiεobutyronitrile (AIBN) . The reaction mixture waε heated at reflux under nitrogen for 1.5 hourε and irradiated with a lamp, the cooled and pour into water (lOOmL) . The organic layer waε separated and washed with H 2 0 (lOOmL) and brine (lOOmL) , dried over MgS0 4 , filtered and concentrated to give a brown solid. Crystallization from ethyl acetate/hexane yielded 2.84g (9.44 mmol) of light brown crystals. The filtrate waε concentrated and the reεidue crystallized from the same solvent syεtem. A second crop of light brown crystalε (0.77g 2.56 mmol) waε obtained. Column chromatography on silica gel of the concentrated filtrate in 20% ethyl acetate/hexanes gave 0.59g (1.96 mmol) of 6-bromomethyl-8- bromoquinoline as a brown solid (4.2g total, 13.95 mmol, 84%), mp 156.2- 157.8°. PREPARATION OF 6- (N-PYRROLIDINYLMETHYL-8-BROMOQUINOLINE Formula 5, Where R 1 Is Pyrrolidinylmethyl and R 2 Is Bromo 0.62g (2.1 mmol) of 6-bromomethyl-8-bromoquinoline was slurried in 15 mL of THF and pyrrolidine (0.38 mL, 4.6 mmol) was added dropwise under nitrogen. The reaction mixture was stirred for 1.5h, and then poured into half saturated NaHC0 3 (50mL) and 25 mL EtOAc. The organic layer was waεhed with H 2 0 (20mL) , and brine (25mL) , dried over MgS0 4 , filtered and concentrated. Flaεh chromatography of the reεidue on εilica gel uεing 5% MeOH/CH 2 Cl 2 yielded 0.44g (1.51 mmol, 72%) of 6- (N-pyrrolidinylmethyl) -8-bromoquinoline aε a dark oil. PREPARATION OF 6- (N-PYRROLIDINYLMETHYL-8- (3-NITROPHENYL)QUINOLINE Formula 5, Where Is Pyrrolidinylmethyl and Is 3-Nitrophenyl 0.32g (1.1 mmol) of 6- (N-pyrrolidinylmethyl) -8-bromoquinoline waε diεεolved in 10 mL of 1:1 EtOH/benzene under nitrogen. 3-nitrophenyl boronic acid (0.37g, 2.2 mmol), 2M Na 2 C0 3 (2.2 mL, 4.4 mmol), and tetrakiε(triphenyl- phoεphine)palladium Pd(PPh 3 ) 4 (0.05g, 0.044 mmol) were added succesεively and the reaction mixture waε refluxed for 4h, then cooled and poured into water (15mL) and extracted with EtOAc (15 mL) . The organic layer waε waεhed with water (10 mL) and brine (lOmL) , dried over MgS0 4 , filtered and concentrated. The reεidue was chromatographed using 10% methanol/ CH 2 C1 2 . 0.29g (0.87 mmol) of 6- (N-pyrrolidinylmethyl) -8- (3-nitrophenyl)quinoline was obtained as a yellow oil. The oil was disεolved in 15 ml of EtOAc, and the HCL salt was formed with a saturated solution of HCl/EtOAc. The residue was concentrated and crystallized from ethanol/ethyl acetate/ether/hexane to give 0.29g (0.71 mmol, 65%) of 6- (N-pyrrolidinylmethyl) -8- (3-nitro¬ phenyl)quinoline dihydrochloride as yellow crystals, mp 223-225°C PREPARATION OF 6- (N-PYRROLIDINONYLMETHYL) -8-BROMOQUINOLINE Formula 5, Where R 1 Is Pyrrolidinonylmethyl and R 2 Is Bromo 8-bromo-6-bromomethylquinoline (1.33 mmol) was dissolved in THF/[1,3- dimethyl-3,4,5,6-tetrahydro-2 (lH)pyrimidinone (DMPU) and reacted with a solution of NaH (1.6 mmol) and pyrrolidinone (1.6 mmol) at reflux for 24 h to obtain 8-bromo-6- (N-pyrrolidinonylmethyl) quinoline as a yellow oil that was used directly in the next step. PREPARATION OF 6- (N-PYRROLIDINONYLMETHYL-8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is Pyrrolidinonylmethyl and R 2 Is 3-Nitrophenyl 8-bromo-6- (N-pyrrolidinonylmethyl) quinoline (1.05 mmol) waε reacted with 3-nitroboronic acid (2.1 mmol), 2M Na 2 C0 3 (4.2 mmol), and Pd(PPh 3 ) 4 (0.04 mmol) to obtain 8- (3-nitrophenyl) -6- (N-pyrrolidinonylmethyl) quinoline as white crystals (0.55 mmol, 52%), mp 127.4-128.3°C EXAMPLE 14 (REACTION SCHEME C-3) PREPARATION OF 6-PYRRO YLMETHYL-8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is Pyrrolylmethyl and R 2 Is 3-Nitrophenyl 0.6g (1.75 mmol) of freshly distilled pyrrole waε added to a εlurry of NaH (0.046g, 1.9 mmol) in 5 mL of dry DMF under nitrogen. The reaction mixture was stirred for 10 min and then 0.6g (1.75 mmol) of 6-bromomethyl-8- (3- nitrophenyl)quinoline, disεolved in 5 mL of DMF, waε added to form a dark solution. The solution was stirred at room temperature for 2h, then heated at 80°C for 2h. The reaction mixture was cooled and poured into 150 mL of water, extracted with CH 2 C1 2 (4 x 25 mL) . The combined organic layers were washed with water (50 mL) , brine (50mL) , and dried over MgS0 4 . Filtration and concentration provided a solid which was purified by flaεh chromatography on silica gel using 30% ethyl acetate/hexane. Yield: 0.3g of a yellow oil. The oil was dissolved in 15 mL of ethyl acetate and the HCl salt was formed from ethyl acetate/HCl. The solution was concentrated and the reεulting oil was crystallized from ethanol/ether . Yield: 0.26g (0.64 mmol, 37%) of 6-pyrrolylmethyl-8- (3-nitrophenyl) quinoline dihydrochloride as yellow crystals, mp 183.2-184.8°C PREPARATION OF 6- (PHENYLAMINOMETHY ) -8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is Phenyla inome hyl and R 2 Is 3-Nitrophenyl 0.5g (1.46 mmol) of 6-bromomethyl-8- (3-nitrophenyl)quinoline was disεolved in lOmL of ethanol. 0.15g (1.61 mmol) of aniline and 0.3g (2.2 mmol) of K,C0 3 waε added. The reaction mixture waε refluxed under nitrogen for 24h, then poured into water (50 mL) and ethyl acetate (50 mL) . The organic layer was separated and washed with water (30 mL) and brine (30 mL) , dried over MgS0 4 , filtered, concentrated and purified by flash chromatography using 30% ethyl acetate/hexane. An impure yellow oil was obtained which waε further purified by preparative TLC using the same solvent syεtem to obtain 0.2g of yellow oil. Crystallization from ethyl acetate/hexane gave O.lg (0.28 mmol, 19%) of 6- (phenylaminomethyl) -8- (3- nitrophenyl)quinoline as yellow crystals, mp 149.9-150.5°C PREPARATION OF 6- (1,2,4- RIAZOLYLMETHYL) -8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is 1,2,4-Triazolylmethyl and R 2 Is 3-Nitrophenyl 6-Bromomethyl-8- (2-nitrophenyl)quinoline (1.75 mmol) was reacted with 1,2,4-triazole (3.5 mmol), K J CO J (4.38 mmol), and tetrabutylammonium iodide (0.18 mmol) in refluxing ethyl acetate to obtain 6- (1,2,4- triazolylmethyl) -8- (3-nitrophenyl)quinoline (0.91 mmol, 57%) aε yellow cryεtals, mp 160.7-161.5°C PREPARATION OF 6- (1,2,4-TRIAZOLYLMETHYL) -8- (3-CHLOROPHENYL)QUINOLINE Formula I, Where R 1 Is 1,2,4-Triazolylmethyl and R 2 Is 3-Chlorophenyl 6-Bromomethyl-8- (3-chlorophenyl)quinoline (1.26 mmol) was reacted with a solution of NaH (1.89 mmol) and 1,2,4-triazole (1.89 mmol), in THF for 24h to give 6- (1,2,4-triazolylmethyl) -8- (3-chlorophenyl) quinoline dihydrochloride (0.22 mmol, 18%) aε light brown crystalε, mp 208.1-208.5°C PREPARATION OF 6- (IMIDAZOLYLMETHYL) -8- (3-CHLOROPHENYL)QUINOLINE Formula I, Where R 1 Is Imidazolylmethyl and R 2 Is 3-Chlorophenyl 6-Bromomethyl-8- (3-chlorophenyl) quinoline (1.7 mmol) was reacted with a εolution of ε-BuLi (1.7 mmol) and imidazole (1.87 mmol) in THF at -78°C, then room temperature for lh to obtain 6- (imidazolylmethyl) -8- (3- chlorophenyl) quinoline dihydrochloride (1.35 mmol, 79 %) , mp 65-65.4°C PREPARATION OF 6- (IMIDAZOLYLMETHYL) -8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is Imidazolylmethyl and R 2 Is 3-Nitrophenyl 6-Bromomethyl-8- (3-nitrophenyl)quinoline (1.28 mmol) waε reacted with a solution of n-BuLi (1.92 mmol) and imidazole (1.92 mmol) in THF at -78° C, then room temperature for 24 h to give 6- (imidazolylmethyl) -8- (3- nitrophenyl)quinoline (0.52 mmol, 40%), mp 129.5-130.5°C EXAMPLE 15 (REACTION SCHEME C-l) PREPARATION OF 6- (4-FLUOROBENZYL) -8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is 4-Fluorobenzyl and R 2 Is 3-Nitrophenyl 0.5g (1.46 mmol) of 6-bromomethyl-8- (3-nitrophenyl)quinoline was dissolved in 15 mL of 1:1 ethanol/benzene. 0.41g ( 2.9 mmol) of 4-fluorophenyl boronic acid, 3 mL (5.8 mL) 2M and 0.07g (0.06 mmol) Pd(PPh 3 ) 4 were added. The reaction mixture was refluxed under nitrogen for 20 min, cooled and poured into water (30 mL) and extracted with ethyl acetate (30 mL) . The organic layer was washed with water (25 mL) and brine (25 mL) , dried over MgS0 4 , filtered and concentrated. The residue was purified by flash chromatography using 30% ethyl acetate/ hexane to obtain 0.41g of an impure yellow oil which was further purified by preparative TLC using the εame εolvent system. 0.33g of a clear oil was obtained which was crystallized from ethyl acetate/hexanes at 0° C to give 0.2g (0.56 mmol, 36%) of 6- (4- fluorobenzyl) -8- (2-nitrophenyl)quinoline as white cryεtalε, mp 97.7-98.5°C PREPARATION OF 6- (4-METHOXYBENZYL) -8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is 4-Methoxybβnzyl and R 2 Is 3-Nitrophenyl 6-Bromomethyl-8- (3-nitrophenyl)quinoline (1.17 mmol) waε reacted with 4- methoxyboronic acid (2.34 mmol), 2M Na 2 C0 3 (4.68 mmol), and Pd(PPh 3 ) 4 (0.05 mmol) to obtain 6- (4-methoxybenzyl) -8- (3-nitrophenyl)quinoline (0.49 mmol, 42%) aε tan cryεtals, mp 117.5-119.1°C. EXAMPLE 16 (REACTION SCHEME B-1) PREPARATION OF 6-ISOPROPYL-8-(3,4-METHYLENEDIOXYPHENYL)QUINOLINE Formula I, Where R 1 Is Isopropyl and R 2 Is 3,4-Methylenedioxyphenyl 0.84g (3.36 mmol) of 6-isopropyl-8-bromoquinoline was diεsolved in 15 mL of dry THF and cooled to -78°C s-BuLi ( 2.7 mL, 3.53mmol, (1.3M/cyclohexane) ) was added dropwise under nitrogen. The reaction mixture was stirred for 5 min and then ZnCl 2 (7 mL, 3.53 mmol, (0.5M/THF)) was added dropwise. The reaction mixture was warmed to room temperature over a period of 1 h. 0.44mL (3.7 mmol) of l-Bromo-3,4-methylenedioxybenzene was added dropwise followed by 0.19g ( 0.17mmol) Pd(PPh 3 ) 4 . The reaction mixture was refluxed for 2.5 h, cooled and poured into water (25 mL) and ethyl acetate (25 mL) . The organic layer was waεhed with water (20 mL) and brine (20 mL) , dried over MgS0 4 , filtered and concentrated. The resulting brown oil waε purified by flash chromatography using 15% ethyl acetate /hexanes to obtain 0.47g of a pure, clear oil which was crystallized from ethyl acetate/hexanes. Yield: 0.25g (0.85 mmol, 25%) of 6-isopropyl-8- (3,4-methylenedioxy- phenyl)quinoline as white platelets, mp 86.6-88.2°C PREPARATION OF 6-ISOPROPYL-8- (3-CYANOPHENYL)QUINOLINE Formula I, Where R 1 Is Isopropyl and R 2 Is 3-Cyanophenyl 6-Isopropyl-8-bromoquinoline (3.8 mmol) waε reacted with 1.3M ε-BuLi (3.99 mmol), ZnCl 2 (3.8 mmol), 3-cyanobromobenzene (3.8 mmol), and Pd(PPh 3 )4 (0.19 mmol) to obtain 6-iεopropyl-8- (3-cyanophenyl)quinoline dihydrochloride (1.1 mmol, 29%) aε white cryεtalε, mp 194.8-197.6°C PREPARATION OF 6-ISOPROPYL-8- (4-METHOXYPHENYL)QUINOLINE Formula I, Where R 1 Is Isopropyl and R 2 Is 4-Me hoxyphenyl 6-Isopropyl-8-bromoquinoline (3 mmol) was reacted with 1.3M s-BuLi (3.03 mmol), ZnCl 2 (3 mmol), 4-methoxyiodobenzene (3.6 mmol), and Pd(PPh 3 ) 4 (0.15 mmol). 6-iεopropyl-8- (4-methoxyphenyl)quinoline (0.67 mmol, 23%) was obtained aε a clear oil. PREPARATION OF 6-ISOPROPYL-8- (4-TRIFLUOROMETHYLPHENYL)QUINOLINE Formula I, Where R 1 Is Isopropyl and R 2 Is 4-Trifluoromethylphenyl 6-Isopropyl-8-bromoquinoline (2.7 mmol) was reacted with 1.3M s-BuLi (2.83 mmol), ZnCl, (2.83 mmol), 4-trifluoromethyliodobenzene (4.05 mmol), and Pd(PPh 3 ) 4 (0.14 mmol) to obtain 6-isopropyl-8- (4- trifluoromethylphenyl)quinoline hydrochloride (0.97 mmol, 36 %) as off- white crystalε, mp 167.5-168.4°C. EXAMPLE 17 (REACTION SCHEME B) PREPARATION OF METHYL 3-TRIFLUOROMETHANESULFOXYBENZOATE Formula 3C, Where R 2 Is Trifluoro ethanesulfonyloxy lOg (65.73 mmol) of Methyl 3-hydroxybenzoate waε diεεolved in 330 mL of CH 2 C1 2 and cooled to 0°C. 45.8 mL (328.65 mmol) of triethylamine waε added to form a light brown solution. Trifluoromethanesulfonic anhydride (triflie anhydride) ( 16.6 mL, 98.6 mmol) was added via addition funnel under nitrogen over 0.5h to form a dark brown solution. The reaction mixture was poured into a saturated solution of NaHC0 3 (200 mL) and extracted with CH 2 C1 2 (200 mL) . The organic layer was waεhed with water (2 x lOOmL) and brine (100 mL) , dried over MgS0 4 , filtered, and concentrated. Flaεh chromatography using 20% ethyl acetate/ hexanes provided a εlightly impure brown oil which waε distilled (1.2 torr, 92-94.5°C) to yield 13.79g ( 48.52 mmol, 74%) of 3- (trifluoromethanesulfonyloxy)benzoic acid methyl ester (methyl 3-trifluoromethanesulfoxybenzoate) as a yellow liquid. PREPARATION OF 6-ISOPROPYL-8- (3-CARBOMETHOXYPHENYL)QUINOLINE Formula I, Where R 1 Is Isopropyl and R 2 Is 3-Methylbenzoate 6-Isopropyl-8-bromoquinoline (4.12 mmol) waε reacted with 1.3M s-BuLi (4.33 mmol), ZnCl 2 (4.33 mmol), methyl 3-trifluorosulfoxybenzoate (4.33 mmol), and Pd(PPh 3 ) 4 (0.21 mmol) to obtain 6-isopropyl-8- (3-carbomethoxy- phenyl)quinoline hydrochloride (0.56g, 1.64 mmol, 40%) which waε cryεtallized from ethanol/ether/hexaneε to yield light yellow cryεtals, mp 166.5-167.6°C EXAMPLE 18 (REACTION SCHEME C-l) PREPARATION OF 6-CYANOMETHYL-8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is Cyanomethyl and R 2 Is 3-Nitrophenyl lg (2.91 mmol) of 6-Bromomethyl-8- (3-nitrophenyl) quinoline was disεolved in 5mL of CH 2 C1 2 . To thiε εolution waε added dropwiεe 0.78g (2.91 mmol) of tetrabutylammonium cyanide dissolved in 5 ml of CH 2 C1 2 over 5 min. The reaction mixture was stirred for lh at room temperature then refluxed overnight. An additional 0.39g (1.45 mmol) of tetrabutylammoniun cyanide was added and the reaction refluxed for 3 more hourε. The reaction was then concentrated and ethyl acetate (30 mL) and water (30 mL) were added. The organic layer waε washed with water (2 x 30 mL) , and brine (30 mL) . CH 2 C1 2 (50 mL) was added to the organic layer to solubilize the suspended solidε and the εolution waε then dried over MgS0 4 filtered and concentrated. The residue was disεolved in a minimal amount of CH,C1 2 , abεorbed on εilica gel, and placed on top of a εilica gel column and eluted with 50% ethyl acetate/ hexaneε. Yield 0.6g (2.07 mmol, 71%) of 6-cyanomethyl-8- (3- nitrophenyl) quinoline aε a yellow solid, mp 178.0-180 ,5°C. PREPARATION OF 6- [1- (4-CHLOROPYRIDAZ NYL) -1-CYANOMETHYL] -8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is [1- (4-Chloroρyridazinyl) -1-cyanomethyl] and R 2 Is 3- Nitrophenyl 0.45g (1.56 mmol) of 6-cyanomethyl-8- (3-nitrophenyl)quinoline and 0.49 (3.28 mmol) of 1,4-dichloropyridazine were dissolved in 15 mL of dry DMF under nitrogen and cooled to 0 C. NaH (0.078g 3.28 mmol) was added portionwise and the reaction stirred at 0 C for 45 min and then 30 min at room temperature. The reaction mixture was poured into CH 2 C1 2 (150 mL) and 150 mL of half saturated NH 4 C1 waε added. The organic layer was separated and the aqueous layer was washed with CH 2 C1 2 (100 mL) . The combined organic layers were waεhed with water (2 x 100 mL) , and brine (100 mL) , dried over MgS0 4 , filtered and concentrated. Chromatography using 50% ethyl acetate/ hexanes yielded 0.51g (1.27 mmol, 81%) of 6- (1- (4-chloropyridazinyl) -1- cyanomethyl) -8- (3-nitrophenyl)quinoline as an orange foam. PREPARATION OF 6-PYRIDAZINONYLMETHYL) -8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is Pyridazinonylmethyl] and R 2 Is 3-Nitrophenyl 0.4g (l mmol) of 6- (1- (4-chloropyridazine) -1-cyanomethyl) -8- (3- nitrophenyl)quinoline was dissolved in 5 mL acetic acid, 5 mL water, and 10 mL cone, hydrochloric acid. The reaction mixture was refluxed for 24h, and then concentrated. The residue was dissolved in water (25 mL) , saturated NaHC0 3 (150 mL) and ethyl acetate (100 mL) were added. The organic layer waε waεhed with water (100 mL) and brine (100 mL) , dried over MgS0 4 , filtered and concentrated to obtain 0.27g of a brown εolid. The residue was purified by preparative TLC using 5% MeOH/ CH 2 C1 2 . Yield: 0.25g (0.7 mmol, 70%) of 6- (4-pyridazinonylmethyl) -8- (3-nitrophenyl)quinoline as an off-white solid, mp 199.5-202.0° C. EXAMPLE 19 (REACTION SCHEMES A-l, B) PREPARATION OF 4-NITRO-1-CYCLOPENTYLIDINYLBENZENE Formula la. Where R Is Cyclopentyl 5g (33.42 mmol) of Cyclopentyltriphenylphosphine bromide waε slurried in lOOmL of dry THF and 18.4 mL of 1.8M PhLi ( 33.09 mmol) was added over 5 min. The reaction mixture waε εtirred for lh at room temperature, then refluxed for 15 min, and cooled to room temperature. 5g (33.09 mmol) of 4- nitrophenyl carboxaldehyde in 40 mL of dry THF was added dropwise. The reaction mixture was stirred at 40° C for 24 h, then poured into water (100 mL) and ethyl acetate (100 mL) . The aqueouε layer waε extracted with ethyl acetate (3 x 50 mL) . The combined organic layers were dried over MgS0 4 , filtered, and concentrated. Flaεh chromatography uεing 50% ethyl acetate/hexanes yielded 4.7 g (23.13 mmol) of 4-nitro-l-cyclo- pentylidinylbenzene as an impure black oil. PREPARATION OF CYCLOPENTYLIDINYLANILINE Formula lb, Where R Is Cyclopentyl 4.7g of 4-nitro-l-cyclopentylidinylbenzene was disεolved in ethanol (100 mL) and catalytically hydrogenated (Pd/C) under 1 atm of hydrogen for 24h. The reaction mixture waε filtered through Celite, concentrated to an orange εemi-εolid, and chromatographed using 10% ethyl acetate to obtain 2.14g (12.35 mmol) of 4-cyclopentylidinylaniline as an yellow semi-solid. PREPARATION OF 4-CYCLOPENTYLMETHYLANILINE Formula 2a, Where R Is Cyclopentyl 1.83g (10.32 mmol) of 4-cyclopentylidinylaniline waε diεεolved in ethanol (50 mL) and catalytically hydrogenated (Pt0 2 ) under 1 atm of hydrogen for 30 min. The reaction mixture was filtered through Celite and concentrated. The residue was chromatographed uεing 20% ethyl acetate/ hexanes to afford 1.52 g of a yellow oil aε a mixture of εtarting material and product. The yellow oil waε diεsolved in ethanol (25 mL) and catalytically hydrogenated (Pt0 2 ) under 1 atm of hydrogen for 5h. Filtration through Celite, concentration, and chromatography uεing 20% ethyl acetate/ hexanes gave 1.52g (8.67 mmol 84%) of 4-cyclopentylmethylaniline as a clear oil. PREPARATION OF 2-BROMO-4-CYCLOPENTYLMETHYLANILINE Formula 3a, Where R Is Cyclopentyl and X is Bromo 1.07g (6.1 mmol) of 4-cyclopentylmethylaniline was disεolved in DMF (2.5 mL) and placed under nitrogen. 1.09g (6.1 mmol) of N-bromosuccinamide, dissolved in DMF (2.5 mL) , was added dropwise. The reaction mixture was stirred for 5h, then poured into water (100 mL) , and extracted with ether (3 x 25 mL) . The combined ether extracts were dried over MgS0 4 and filtered. Concentration and flaεh chromatography on εilica gel using 10% ethyl acetate/hexanes provided 0.98g (3.86 mmol, 63%) of 2-bromo-4-cyclopentylmethylaniline as a light brown oil. PREPARATION OF 6-CYCLOPENTYLMETHYL-8-BROMOQUINOLINE Formula 5, Where R Is Cyclopentylmethyl and X is Bromo 0.66g (2.6 mmol) of 2-bromo-4-cyclopentylmethylaniline was εlurried in 0.094g (0.34 mmol) Iron (II) sulfate heptahydrate, 0.17 mL (1.66mmol) nitrobenzene, and lg (10.4 mmol) of glycerol, and heated to 115°C under nitrogen. H 2 S0 4 (0.55 mL) waε added dropwiεe and the reaction mixture was heated to 165°C, stirred for 2h and then poured into saturated NaHC0 3 (300 mL) and ethyl acetate (50 mL) . The solution was filtered through glass wool and the filtrate was extracted with ethyl acetate (2 x 50mL) . The combined extracts were dried over MgS0 4 and filtered. Concentration and flash chromatography (10% EtOAc/hexanes) yielded 0.58g (2 mmol, 77%) of 6- cyclopentylmethyl-8-bromoquinoline as a yellow oil. PREPARATION OF 6-C CLOPENTYLMETHYL-8- (3-CHLOROPHENYL)QUINOLINE Formula I, Where R 1 Is Cyclopentylmethyl and R 2 is 3-Chlorophenyl 0.19g (0.65 mmol) of 6-Cyclopentylmethyl-8-bromoquinoline was dissolved in 6.5 mL of 1:1 ethanol/ benzene under nitrogen. 0.2g (1.3 mmol) of 3- chloroboronic acid, 1.3 mL (2.6 mmol) of 2M Na 2 C0 3 , and 0.03g (0.026 mmol) of Pd(PPh 3 ) 4 were added succesεively. The reaction mixture was refluxed for 3h, then cooled and poured into water (25 mL) and ethyl acetate (25 mL) . The organic extract was dried over MgS0 4 and filtered. Flash chromatography on silica gel using 20% ethyl acetate/hexanes yielded 0.17g of impure product which waε purified further by preparative TLC in the same εolvent system to obtain 0.16g yellow oil. Formation of the HCl salt with saturated HCl/EtOAc and crystallization of the resulting residue from EtOH/EtOAc/ether yielded 0.14 g (0.4 mmol, 60%) of 6-cyclopentylmethyl-8- (3-chlorophenyl) quinoline hydrochloride as white crystals, mp 179.3- 183.7°C. PREPARATION OF 6-CYCLOPENTYLMETHYL-8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is Cyclopentylmethyl and R 2 is 3-Nitrophenyl Similarly, 6-Cyclopentylmethyl-8-bromoquinoline (0.55 mmol) was reacted with 3-chloroboronic acid (1.1 mmol), 2M Na 2 C0 3 (2.2 mmol), and Pd(PPh 3 ) 4 (0.02 mmol) to obtain 6-cyclopentylmethyl-8- (3-nitrophenyl) quinoline hydrochloride (0.42 mmol, 77 %) , as tan crystals from EtOH/EtOAc/Et 2 0, mp 185.8-190.4°C EXAMPLE 20 (REACTION SCHEMES B-3, B) PREPARATION OF 6-METHOXY-8-AMINOQUINO INE Formula 5, Where R 1 Is Methoxy and X is Amino 4 g (19.6 mmol) of commercially available 6-methoxy-8-nitroquinoline was diεεolved in ethanol (100 mL) and THF (25 mL) and catalytically hydrogenated (Pd/C, 1 atm H2) for 5h. The reaction mixture was filtered through Celite and concentrated. Flaεh chromatography using 5% MeOH/ CH 2 C1 2 yielded an impure product which was re-chromatographed in 50% EtOAc/hexanes to give 2.76g (15.84 mmol, 81%) of 6-methoxy-8-aminoquinoline aε a yellow oil. PREPARATION OF 6-METHOXY-8-BROMOQUINOLINE Formula 5, Where R 1 Is Methoxy and X is Bromo 1.25 g (7.18 mmol) of 6-methoxy-8-aminoquinoline waε mixed with 48% HBr (6 mL) and water (6 mL) to form an orange εlurry. The mixture was then cooled to 0 C and a solution of 5 g of NaN0 2 (9.3 mmol) in 5 mL of water was added dropwiεe. The reεulting brown εolution waε εtirred for 15 min and then added to a εolution of 1.24 g CuBr (8.6 mmol) in 15 mL of 48% HBr with εtirring at 75°C The reaction mixture was stirred at 75°C for 5.5h and was then made baεic with 10% NaOH and filtered through filter paper. The filtrate waε partitioned between water (50 mL) and EtOAc (50 L) and extracted with EtOAc (2 x 50 mL) . The combined organic extractε were dried over MgS0 4 , filtered, and concentrated to give 0.6 g of a dark oil which waε purified by preparative TLC (20% EtOAc/hexanes) to afford 0.36g (1.5 mmol, 21%) of 6-methoxy-8-bromoquinoline aε a tan εolid, mp 64.5-65.6°C PREPARATION OF 6-HYDROXY-8-BROMOQUINOLINE Formula 5, Where R 1 Is Hydroxy and X is Bromo 0.26g ( 1.1 mmol) of 6-methoxy-8-bromoquinoline was disεolved in CH 2 C1 2 (11 mL) and cooled to -78°C 2.7 mL (2.75 mmol) of BBr 3 (1M in Cϊ^Cl^ was added dropwise to form a yellow slurry. The reaction mixture was stirred for 10 min at -78°C, the bath was removed and the reaction mixture was allowed to warm to room temperature, stirred for 1.5 h and then MeOH (20 mL) was added to quench the reaction. The reaction mixture was concentrated under reduced presεure, 20 mL of MeOH waε added and again concentrated (repeated 2x) . The reεidue waε partitioned between EtOAc and water. The organic layer waε washed 2x with NaOH (0.5 N) . The base extractε were neutralized with saturated NH 4 C1 and extracted with EtOAc (2 x 25 mL) . The organic layers were washed with brine, dried over MgS0 4 , filtered, and concentrated to yield O.llg (0.49 mmol, 45 %) of 6-hydroxy-8-bromoquinoline as an off-white εolid, mp 249.5-250.6°C PREPARATION OF 6-CYCLOPENTYLOXY-8-BROMOQUINOLINE Formula 5, Where R 1 Is Cyclopentyloxy and X is Bromo 0.2g (0.89 mmol) of 6-hydroxy-8-bromoquinoline waε dissolved in DMF (5 mL) . 0.25g (1.78 mmol) of powdered -CjCCj and 0.2 mL(1.78 mmol) cyclopentylbromide were added, and reaction mixture waε heated at 75°C for 1.5h. The reaction mixture waε then cooled and poured into water (20 mL) and extracted with ether (20 mL) . The ether layer was washed with water (30 mL) and brine (30 mL) . The aqueouε layers were re-extracted with ether (20 mL) and the combined organic layers were dried over MgS0 4 , filtered and concentrated to obtain 0.26g (0.89 mmol, 100%) of 6-cyclopentyloxy 8- bromoquinoline as a crude yellow solid, mp 76.2-79.2°C PREPARATION OF 6-CYCLOPENTYLOXY-8- (3-NITROPHENYL)QUINOLINE Formula I, Where R 1 Is Cyclopentyloxy and R 2 is 3-Nitrophenyl 0.22g (0.75 mmol) of 6-cyclopentyloxy-8-bromoquinoline was disεolved in 7.5 mL of 1:1 EtOH/benzene and 0.25g (1.5 mmol) 3-nitroboronic acid, 1.5 mL (3 mmol) 2M Na 2 C0 3 , and 0.035g (0.3 mmol) Pd(PPh 3 ) 4 were added εucceεsively. The reaction mixture was refluxed for 2h under nitrogen, then partitioned between water/EtOAc. The organic layer waε washed with water, brine, dried over MgS0 4 , and filtered. Concentration and purification by preparative TLC using 15% EtOAc/hexaneε provided 0.2g of a yellow oil. The hydrochloride εalt was formed with saturated HCl/EtOAc and crystallized from EtOH/EtOAc/ether. Yield: 0.21g (0.56 mmol, 75%) of 6-cyclopentyloxy-8- (3- j nitrophenyl)quinoline as white crystalε, mp 190-191.4°C EXAMPLE 21 By following the procedureε in Exampleε 1-20, other 6,8-diεubstituted quinolines within the scope of thiε invention can be prepared. For example, the following 6,8-diεubεtituted quinoline compounds of formula I were prepared by following the above described procedures: 6-isopropyl-8- (3-nitrophenyl) quinoline, (hydrochloride) , mp 204.5-216 °C; 4-pyridylmethyl-8- (3-nitrophenyl)quinoline, (dihydrochloride) , mp 238-240°C; 6- [1- (1,2,4-triazolyl) ] -8- (3-nitrophenyl) quinoline, mp 160.7-162.5°C; 6-anilinomethyl-8- (3-nitrophenyl)quinoline, mp 149.9-150.5°C; 6- (4-pyridazinonylmethyl) -8- (3-nitrophenyl)quinoline, mp 199.5-202°C; 6- (2-pyrrolidinonylmethyl) -8- (3-nitrophenyl) quinoline,mp 127.4-128.3°C 6-cyclopentylmethyl-8- (3-nitrophenyl)quinoline, (hydrochloride) , mp 186.3-191.2°C 6-imidazolylmethyl-8- (3-nitrophenyl) quinoline, mp 129.5-130.5°C 6-cyclohexyl-8- (3-nitrophenyl)quinoline, (hydrochloride) , mp 188.5-194.8°C 6-cyclopentyloxy-8- (3-nitrophenyl)quinoline, (hydrochloride) , mp 190-191.4°C 6-ethyl-8- (3-nitrophenyl)quinoline, (hydrochloride) , mp 193.1-193.6°C 6-n-propyl-8- (3-nitrophenyl) quinoline, (hydrochloride) , mp 208.5-209.7°C 6-n-butyl-8- (3-nitrophenyl)quinoline, (hydrochloride) , mp 194.1-198.5°C. 6-t-butyl-8- (3-nitrophenyl)quinoline, (hydrochloride), mp 214-214.8°C; 6-n-pentyl-8- (3-nitrophenyl)quinoline, (hydrochloride) , mp 175.9-177.9°C; 6- (4-fluorobenzyl) -8- (3-nitrophenyl) quinoline, mp 97.7-98.5°C 6-pyrrolidinyl-8- (3-nitrophenyl) quinoline, (dihydrochloride) mp 223-225°C. 4-pyridylmethyl-8- (3-chlorophenyl)quinoline, (dihydrochloride) , mp 243.0-246.4°C; 6- [1- (1,2,4-triazolyl)] -8- (3-chlorophenyl) quinoline, (dihydrochloride) , mp 208.1-208.5°C; 6-imidazolylmethyl-8- (3-chlorophenyl) quinoline, (dihydrochloride) , mp 64-64.5°C 6-ethyl-8- (3-chlorophenyl)quinoline, (hydrochloride) , mp 184.8-185.9°C 6-n-propyl-8- (3-chlorophenyl)quinoline, (hydrochloride), mp 206.4-210.4°C 6-n-butyl-8- (3-chlorophenyl) quinoline, (hydrochloride) , mp 202.3-208.7°C 6-t-butyl-8- (3-chlorophenyl)quinoline, (hydrochloride) , mp 197.5-198.5°C; 6-n-pentyl-8- (3-chlorophenyl)quinoline, (hydrochloride) , mp 182.2-183.6°C; 6-cyclohexyl-8- (3-chlorophenyl) quinoline, (hydrochloride) , mp 197.7-203.7°C. 6- (1-hydroxy-1-methylethyl) -8- (3-chlorophenyl)quinoline, (hydrochloride) , mp 171.2-171.9°C 6-iεopropyl-8- (3,4-methylenedioxyphenyl) quinoline, (hydrochloride) , mp 86.6-88.2°C 6-iεopropyl-8- (3-carbomethoxyphenyl)quinoline, (hydrochloride) , mp 166.5-167.6°C 6-n-propyl-8-phenylquinoline, (hydrochloride) , mp 168-169°C 6-isopropyl-8-phenylquinoline, (hydrochloride), mp 155-158.9°C 6-n-pentyl-8-phenylquinoline, (hydrochloride), mp 151.5-152.3°C 6-isopropyl-8- (4-trifluoromethylphenyl) quinoline, (hydrochloride) , mp 167.5-168.6°C 6-isopropyl-8- (3-cyanophenyl) quinoline, (hydrochloride) , mp 206.5-207.6°C EXAMPLE 22 Determination of Potency and Selectivity of Inhibitors for PDE IV Preparation of Human Platelet Phosphodiesterase (PDE III) Platelet high-affinity cAMP PDE (PDE III) was obtained from human blood in accordance with previously described procedureε described in Mol . Pharmacol . 20:302-309, Alvarez, R., Taylor, A., Fazarri, J.J., and Jacobs, J.R. (1981) . Blood was collected into evacuated tubeε containing EDTA (7.7 mM, final concentration) . PRP waε obtained by centrifuging the blood in polycarbonate tubeε at 200 x g for 15 min at 4°C A platelet pellet waε resuspended in a volume of buffer A (0.137 M NaCl, 12.3 mM Tris-HCl buffer, pH 7.7, containing 1 mM MgCl 2 . The hypotonically-lysed platelet suspension was centrifuged at 48,000 x g for 15 min and the supernatant was saved. The pellets were frozen on dry ice and briefly thawed at 22°C The supernatant was combined with the pellet fraction and the reεulting εuspension waε centrifuged at 48,000 x g for 30 min. The εupernatant fraction waε stored in 0.5 mL aliquotε at -20°C and uεed aε the εoluble PDE. Enzyme activity waε adjuεted to 10-20% hydrolysis after 10 minutes of incubation by dilution with lOmM cold Tris-HCl buffer, pH7.7. Preparation of Human Lymphocyte Phosphodiesterase (PDE IV) Human B cell line (43D) were cultured at 37°C in 7% C0 2 in RPMI 1640 with L-glutamine and 10% Nu-Serum. Prior to the asεay -1.5x10 s cellε were centrifuged at 1000 rpm for 10 minutes in a table top clinical centrifuge. The pellet was reεuspended in 2-3 mL of 45 mM Triε-HCl buffer, pH 7.4. The εuspension was homogenized and centrifuged at 12,000 x g at 4°C for 10 minutes. The supernatant waε diluted to 28 mL with Triε-HCl buffer and uεed directly in the aεεay or stored at -20°C The final concentration of DMSO in the PDE incubation medium was 1%. Nitraquazone waε included in each assay (10 and lOOμM) as a reference standard. Human Platelet cAMP Phosphodiesterase Assay The phosphodieεteraεe incubation medium contained 10 mM Triε-HCl buffer, pH 7.7, 10 mM MgS0 4 , 0.1-lμM [ 3 H] -AMP (0.2 μCi) in a total volume of 1.0 mL. Following addition of the enzyme, the contentε were mixed and incubated for 10 min at 30°C The reaction was terminated by immersing the tubes in a boiling-water bath for 90 sec. After the tubes were cooled in an ice-water bath, 0.1 mL (lOOμg) of 5' -nucleotidase from εnake venom (Crotaluε atrox, Sigma V-7000) waε added to each tube. The contentε were mixed and incubated for 30 min at 30°C The nucleotidase reaction was terminated by immersing the tubeε in a boiling water bath for 60 sec. Labeled adenoεine waε isolated from alumina columns according to the method deεcribed in Anal. Bioche . , 52:505-516 (1973), Filburn, C.R., and Karn, J.. Aεεays were performed in triplicate. Hydrolyεiε of cAMP ranged from 10-20%. Test compounds were dissolved in DMSO. The final concentration of DMSO in the phosphodiesterase assay was 1% when tested with compounds up to 0.1 mM. When tested at 1 mM the DMSO concentration was 10% and this activity was compared to control PDE activity in the presence of 10% DMSO. PDE III Activity Compound I IC^: 53 μM Compound I is 6- (4-pyridylmethyl) -8- (3-nitrophenyl) quinoline. Human Lymphocyte cAMP Phosphodiesterase Assay The phosphodiesteraεe incubation medium contained 40 mM Tris-HCl buffer, pH 7.7, 0.1 mM MgS0 4 , 3.75 mM mercaptoethanol, and 0.1-1.0 μM [ 3 H] cAMP (0.2 μCi) in a total volume of 1.0 mL. The reaction was performed and proceεεed according to the procedure uεed (above) for human platelet PDE. The final concentration of DMSO waε 1%. The representative compounds of the present invention exhibit potency and selectivity as inhibitors of PDE IV when tested by the human platelet cAMP phosphodieεteraεe aεεay and the human lymphocyte cAMP phoεphodiesterase assay. Inhibition of Human Lymphocyte PDE IV Compound I IC.*,: O.023 nM Compound II IC 50 : 0.11 nM Compound III IC^: 0.063 nM Compound I is the compound of Formula I where R 1 iε 4-pyridylmethyl and R 2 iε 3-nitrophenyl, namely 6- (4-pyridylmethyl) -8- (3-nitrophenyl)quinoline. Compound II iε the compound of Formula I where R 1 iε 4-pyridylmethyl and R 2 iε 3-chlorophenyl, namely 6- (4-pyridylmethyl) -8- (3- chlorophenyl) quinoline. Compound III iε the compound of Formula I where R 1 iε iεopropyl and R 2 iε 3-nitrophenyl, namely 6-iεopropyl-8- (3- nitrophenyl)quinoline. EXAMPLE 23 Determination of Immunosuppressive Activity Utilizing Responses of Human Peripheral Blood Lymphocytes to Mitogen This procedure is a modification of a procedure initially described by Greaveε, et al. ["Activation of human T and B lymphocytes by polyclonal mitogens," Nature, 248, 698-701 (1974)] . Human mononuclear cellε (PBL) were εeparated from heparinized whole blood by denεity gradient centrifugation in Ficoll-Paque (Pharmacia) . After washing, 5 x 10 4 cells/well were cultured in microtiter plateε with minimal eεεential media εupplemented with 1% human εerum, gentamicin, εodium bicarbonate, 2-mercaptoethanol, glutamine, non-essential amino acids, and sodium pyruvate. The mitogen concanavalin A (Sigma) was used at a concentration of 2 μg/ml. Test materials were tested at concentrations between 10"* and 10" 10 M, by addition to the culture at time 0. Cultures were set up in quadruplicate and incubated at 37°C in a humidified atmosphere with 5% C0 2 for 48 hours. A pulεe of 1.0 μCi/well of 3 H-thymidine waε added for the last 4 hours. Cells were collected on glass fiber filters with an automatic harvester and radioactivity was measured by standard scintillation procedureε. The 50% inhibitory concentration ("ICV) for mitogenic εtimulation was determined graphically. The representative compounds of the present invention showed immunosuppreεεive activity when teεted by thiε method. EXAMPLE 24 Determination of Immunosuppressive Activity Utilizing The Hemolytic Plaque Forming Cell Assay This procedure iε a modification of "The agar plaque technique for recognizing antibody producing cellε, " a procedure initially deεcribed by Jerne, et al. [Cellbound Antibodies, Amoε and Kaprowεki editorε (Wiεtar Inεtitute Preεε, Philadelphia, 1963) p. 109] . Groups of 5-6 adult C3H female mice were εenεitized with 1.25 x 10 8 εheep red blood cellε (SRBC) and εimultaneouεly treated with an oral doεage form of the teεt material in an aqueouε vehicle. Animalε in a control group received the same volume of vehicle. Four days after SRBC inoculation, spleens were dispersed in glasε homogenizerε. The number of nucleated cellε (WBC) waε determined and the εpleen cell suspension was mixed with SRBC, guinea pig complement and agar solution at 0.5% concentration. Aliquotε of the above mixture (0.1 mL) were dropped on four εeparate quadrantε of a Petri diεh and were covered with cover εlipε. After two hours incubation at 37°C, areas of hemolysis around plaque-forming cellε (PFC) were counted with a diεεecting microεcope. Total WBC/spleen, PFC/spleen and PFC/10 6 WBC (PPM) were calculated for each mouse spleen. Geometric meanε of each treatment group were then compared with the vehicle-treated control group. The repreεentative compoundε of the preεent invention showed immunosuppressive activity when tested by this method. ΞXAMPLE 25 Determination of Anti-Inflammatory Activity Utilizing Arachidonic Acid-Induced Ear Edema (AAEE) in the Mouse This procedure is a modification of a procedure described by Young et al., J. Invest. Derm., 82:367-371 (1984) . Female Charles River ICR mice 23-27 grams were administered 0.2 mL of test material. The mice were challenged with 20 μl of arachidonic acid applied topically to the ear. One hour after challenge, the weight of an 8 mm disc was determined. The mean increase in ear plug weight was calculated. Materials with anti-inflammatory activity inhibit the increase in ear plug weight. The representative compounds of the present invention exhibited anti-inflammatory activity when tested by this method. Anti-inflammatory Activity (AAEE) Compound I Compound II Compound III EXAMPLE 26 Determination of Anti-Inflammatory Activity Utilizing Adjuvant-Induced Arthritis In The Rat This procedure is a modification of a procedure initially described by Pearson, CM., Proc. Soc. Exp. Biol . Med. , 91:95-101 (1956). Female Charles River albino rats weighing 160-180 g received 0.1 mL of a suspenεion in paraffin oil of heat-killed Λfycobacterium butyricum (10 mg/ml) by meanε of an intradermal injection into the proximal 1/4 of the tail on day 0. Beginning on day 1, the teεt material waε adminiεtered orally in an aqueouε vehicle (0.5 mL/dose) once each day for 17 days. On day 18 the intensity of the swelling of the four foot pads and tail waε determined utilizing a εcoring εyεtem in which the εwelling in the four pawε waε εcored 0-4 for each paw and the tail swelling was scored 0-3, such that the total maximum score waε 19. The representative compounds of the present invention exhibited anti-inflammatory activity when tested by this method. EXAMPLE 27 Determination of Activity Towards Autoimmune Disease Utilizing Survival of MRL/lpr Mice MRL/lpr mice develop a multiεyεtemic disease characterized by glomerulonephritiε, arthritis, arteritiε, lymphoid hyperplaεia. The length of survival of mice with this disease is approximately one-third that of non-disease developing MRL/n mice. These mice have a high incidence of autoantibodies and the disease process is considered autoimmune in nature as described by Theofilopoulos, et al. , Advances in Immunology, 37:269-390 (1985) . The representative compounds of the present invention significantly extended the lifespan of the MRL/lpr mice. EXAMPLE 28 Determination of Analgetic Activity Utilizing Phenylquinone-Induced Stretching in the Mouse This procedure iε a modification of a procedure described by Hendershot, et al . J. Pharmacol . Exp. Ther. , 125:237-240 (1959) . Groups of 8 Female CD-I mice were administered test materials orally in an aqueous vehicle. At various times following administration of test materials, 0.25 mL of a 0.02% solution of phenylquinone was administered intraperitoneally. The number of stretches for each animal was enumerated over a ten minute period following the phenylquinone administration. Analgetic activity was determined by inhibition of the mean number of stretches. The representative compounds of the present invention εhowed analgetic activity when tested by this method. EXAMPLE 29 Capsule Formulation This example illustrateε the preparation of a repreεentative pharmaceutical formulation for oral adminiεtration containing an active compound of Formula I, e.g., 6-iεopropyl-8- (3-nitrophenyl) quinoline. Ingredients Quantity (mg/capsule) Active compound 200 lactoεe, spray-dried 148 magneεium εtearate 2 The above ingredientε are mixed and introduced into a hard-εhell gelatin capεule. Other compounds of Formula I, εuch as those prepared in accordance with Examples 1-20 can be used as the active compound in the preparation of the orally adminiεtrable formulations of this example. EXAMPLE 30 Oral Formulation This example illustrateε the preparation of a repreεentative pharmaceutical formulation containing an active compound of Formula I, e.g., 6-isopropyl-8- (3-nitrophenyl) quinoline. An suεpenεion for oral adminiεtration iε prepared having the following compoεition: Ingredients Quantity Active compound 1.0 g fumaric acid 0.5 g εodium chloride 2.0 g methyl paraben 0.1 g granulated sugar 25.5 g εorbitol (70% εolution) 12.85 g Veegum K (Vanderbilt Co.) 1.0 g flavoring 0.035 mL coloringε 0.5 mg diεtilled water q.ε. to 100 mL Other compoundε of Formula I, εuch aε thoεe prepared in accordance with Examples 1-20 can be uεed as the active compound in the preparation of the orally administrable formulationε of thiε example. EXAMPLE 31 Tablet Formulation Thiε example illustrateε the preparation of a repreεentative pharmaceutical formulation containing an active compound of Formula I, e.g., 6-iεopropyl-8- (3-nitrophenyl) quinoline. A tablet for oral adminiεtration is prepared having the following composition: Ingredients Quantity (mg/tablet) Active compound 400 corn starch 50 lactoεe 145 magnesium stearate 5 The above ingredientε are mixed intimately and pressed into single scored tablets. Other compoundε of Formula I, εuch aε thoεe prepared in accordance with Exampleε 1-20 can be used as the active compound in the preparation of the tablet formulations of this example. EXAMPLE 32 Injactable Formulation This example illustrates the preparation of a representative pharmaceutical formulation containing an active compound of Formula I, e.g., 6-isopropyl-8- (3-nitrophenyl) quinoline. An injectable preparation is prepared having the following composition: Ingredients Quantity Active compound 0.2 g water (distilled, εterile) q.ε. to 20.0 mL Other compounds of Formula I, such as those prepared in accordance with Examples 1-20 can be uεed aε the active compound in the preparation of the injection adminiεtrable fσrmulationε of this example. EXAMPLE 33 Suppository Formulation This example illuεtrates the preparation of a representative pharmaceutical formulation containing an active compound of Formula I, e.g., 6-iεopropyl-8- (3-nitrophenyl)quinoline. A εuppoεitory totalling 2.5 grams is prepared having the following compoεition: Ingredients Quantity Active compound 500 mg Witepsol H-15" q.s. to 2.5 g ("triglycerideε of saturated vegetable fatty acid; a product of Riches- Nelson, Inc., New York, N.Y.) . Other compoundε of Formula I, εuch aε thoεe prepared in accordance with Exampleε 1-20 can be used aε the active compound in the preparation of the suppository formulations of this example. TOXICOLOGY No serious toxicological effects were observed in the above deεcribed assayε.

Claims: WHAT IS CLAIMED IS: 1. A compound of the formula Formula I wherein: R 1 is εelected from hydrogen; lower alkyl; cycloalkyl; cycloalkyloxy; cycloalkylamino; cycloalkyl lower alkyl; lower alkoxy; formyl; hydroxy-lower alkyl; carboxyalkyl; optionally εubεtituted aryl, aryloxy, arylamino or aryl-lower alkyl; optionally εubstituted heterocycle, heterocycle-oxy, heterocycle-amino or heterocycle- lower alkyl; and R 2 is optionally substituted phenyl, provided that when R 1 iε methoxy, R 2 iε not 4-nitrophenyl or 4- aminophenyl; or a pharmaceutically acceptable εalt or N-oxide thereof. 2. The compound of Claim 1 wherein R 2 iε phenyl subεtituted in the 3-poεition with halo, nitro, cyano, lower alkoxycarbonyl or trifluoromethyl. 3. The compound of Claim 2 wherein R 2 is 3-chlorophenyl, 3-nitrophenyl or 3-cyanophenyl. 4. The compound of Claim 3 wherein R 1 is pyridylmethyl, benzyl, lower alkyl, hydroxy-lower alkyl, or cycloalkylmethyl. 5. The compound of Claim 4 wherein R 1 is 4-pyridylmethyl, benzyl, ethyl, n-propyl, isopropyl, n-butyl, 1-hydroxy-1-methylethyl, cyclopropylmethyl or cyclopentylmethyl. 6. The compound of Claim 1 wherein R 2 is phenyl εubstituted in the 3- and 4-position, independently, with halo, nitro, cyano, lower alkoxycarbonyl, lower alkylenedioxy or trifluoromethyl. 7. The compound of Claim 6 wherein R 2 is 3-chloro-4-fluorophenyl or 3,4-methylenedioxyphenyl. 8. The compound of Claim 7 wherein R 1 is pyridylmethyl, benzyl, lower alkyl, hydroxy-lower alkyl, or cycloalkylmethyl. 9. The compound of claim 8 wherein R 1 is 4-pyridylmethyl, benzyl, ethyl, n-propyl, isopropyl, n-butyl, 1-hydroxy-1-methylethyl, cyclopropylmethyl or cyclopentylmethyl. 10. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of the formula Formu I a I wherein: R 1 is selected from hydrogen; lower alkyl; cycloalkyl; cycloalkyloxy; cycloalkylamino; cycloalkyl lower alkyl; lower alkoxy; formyl; hydroxy-lower alkyl; carboxyalkyl; optionally substituted aryl, aryloxy, arylamino or aryl-lower alkyl; optionally εubstituted heterocycle, heterocycle-oxy, heterocycle-amino or heterocycle- lower alkyl; and R 2 iε optionally substituted phenyl, provided that when R 1 is methoxy, R 2 is not 4-nitrophenyl or 4- aminophenyl; or a pharmaceutically acceptable salt or N-oxide thereof. 11. Uεe of a compound repreεented by the formula Formula I wherein: R' iε εelected from hydrogen; lower alkyl; cycloalkyl; cycloalkyloxy; cycloalkylamino; cycloalkyl lower alkyl; lower alkoxy; formyl; hydroxy-lower alkyl; carboxyalkyl; optionally substituted aryl, aryloxy, arylamino or aryl-lower alkyl; optionally subεtituted heterocycle, heterocycle-oxy, heterocycle-amino or heterocycle- lower alkyl; and R 2 iε optionally εubεtituted phenyl, provided that when R 1 iε methoxy, R 2 iε not 4-nitrophenyl or 4- aminophenyl; or a pharmaceutically acceptable εalt or N-oxide thereof, in the manufacture of a medicament for treating asthma, allergy, rhinitis, atopic dermatitis, pain, inflammatory diseaεe, allograft rejection, graft-vs-host rejection, and autoimmune diseaεe in mammals. 12. A proceεε for the preparation of a compound of the formula Formu I a I wherein: R 1 is selected from hydrogen; lower alkyl; cycloalkyl; cycloalkyloxy; cycloalkylamino; cycloalkyl lower alkyl; lower alkoxy; formyl; hydroxy-lower alkyl; carboxyalkyl; optionally subεtituted aryl, aryloxy, arylamino or aryl lower alkyl; optionally εubstituted heterocycle, heterocycle-oxy, heterocycle-amino or heterocycle lower alkyl; and R 2 is optionally substituted phenyl, provided that when R 1 is methoxy, R 2 iε not 4-nitrophenyl or 4- aminophenyl; or a pharmaceutically acceptable salt or N-oxide thereof, which comprises (a) reacting a compound of the ' formula (4) where R' and R 2 are as defined above, with glycerol in the presence of an oxidant; or (b) reacting a compound of the formula (5) where R 1 is as defined above and X iε chloro, bromo or iodo, with a boronic acid of the formula (3B) R -B(OH) 2 where R 2 iε optionally εubεtituted phenyl; or (c) reacting a compound of the formula where iε aε defined above, with a trifluoromethaneεulfonyloxy benzene of the formula (3C) R 2 -OTf where R 2 is optionally εubεtituted phenyl, and -OTf iε trifluoro¬ methaneεulfonyloxy; or (d) reacting a compound of the formula (5) where R is lower alkyl, cycloalkyl, aryl, or heterocycle, with a boronic acid of the formula (3B) R 2 -B(OH) 2 where R 2 is optionally substituted phenyl; or (e) reacting a compound of the formula (I) where R 2 is optionally substituted phenyl, with a lower alkyl Grignard reagent or a lower alkyl lithium reagent; or (f) reacting a compound of the formula where R 2 is optionally εubstituted phenyl, with a boronic acid of the formula (3B) R-B(OH), where R is cycloalkenyl, aryl or heterocycle; or (g) reacting a compound of the formula where R 2 is optionally εubstituted phenyl, and R is alkyl, cycloalkyl or heterocycle, with a concentrated acid; or (h) reacting a compound of the formula where R j is optionally subεtituted phenyl and X iε chloro, bromo or iodo, with a compound of the formula where R iε lower alkyl, cycloalkyl, aryl or heterocycle; and R 2 is independently lower alkyl or aryl; or NR, is heterocycle; or (i) reacting the free base of a compound of Formula I with an acid to give a pharmaceutically acceptable acid addition salt; or (j) reacting an acid addition salt of a compound of Formula I with a base to give the correεponding free baεe; or (k) converting an acid addition εalt of a compound of Formula I to another pharmaceutically acceptable acid addition εalt of Formula I.

Inventors: CHIN RONNIE LIPP, FATHEREE PAUL ROSS, WILHELM ROBERT STEPHEN, CHIN, RONNIE, LIPP, FATHEREE, PAUL, ROSS, WILHELM, ROBERT, STEPHEN
Applicants: SYNTEX INC, SYNTEX (U.S.A.) INC.
Application year: 1994
Main classification: C07D401
IPC codes: A61K31, A61P11, A61P17, A61P25, A61P27, A61P29, A61P37, A61P43, C07D215, C07D401, C07D405, C07D521